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由留部 崇医学部附属病院 整形外科助教
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■ 受賞- 2023年03月 第35回日本軟骨代謝学会, 第28回学会賞, ラット椎間板恒常性維持へのオートファジーの関与：Atg5に対するRNA干渉を用いた細胞・動物実験による検討
- 2022年10月 神戸大学医学部, 神戸大学医学部優秀学術論文賞, Involvement of autophagy in the maintenance of rat intervertebral disc homeostasis: an in-vitro and in-vivo RNA interference study of Atg5
- 2021年12月 Journal of Orthopaedic Research, Wiley, USA, 2020 Top Reviewers, 2020 Top Reviewers
- 2021年05月 Osteoarthritis and Cartilage, 2020 Top Reviewers, 2020 Top Reviewers
- 2021年04月 第136回中部日本整形外科災害外科学会, 学会奨励賞, ラット椎間板恒常性維持に対するAtg5依存性オートファジーの関与：ラット細胞・動物実験の検討
- 2020年10月 神戸大学医学部, 神戸大学医学部優秀学術論文賞, Reduced nucleotomy-induced intervertebral disc disruption through spontaneous spheroid formation by the Low Adhesive Scaffold Collagen (LASCol)
- 2020年09月 第49回日本脊椎脊髄病学会, 第15回Asia Traveling Fellowship
- 2020年04月 第49回日本脊椎脊髄病学会, 日本脊椎脊髄病学会優秀論文賞, 脊椎転移に対する手術療法の効果と限界
- 2019年11月 The 47th Annual Meeting, Cervical Spine Research Society, 3rd Place Basic Research Paper Award, Involvement of autophagy in human cervical spine degenerated and herniated discs
- 2019年09月 第27回日本腰痛学会, 最優秀演題賞, ラット脊椎椎間板の恒常性維持におけるAtg5依存性オートファジーの関与
- 2018年11月 第2回リハビリテーション医学会秋季学術集会, YIA優秀賞, 70歳以上の脊椎転移患者の手術成績－PS、ADL、QOLの推移から－国内学会・会議・シンポジウム等の賞
- 2018年05月 The 45th Annual Meeting, International Society for the Study of the Lumbar Spine, ISSLS Best Posters 2018, Features and problems of corrective long spinal fusion for adult spinal deformity with multiple vertebral fractures due to severe osteoporosis国際学会・会議・シンポジウム等の賞
- 2018年04月 第130回中部日本整形外科災害外科学会, 学会奨励賞, 前向きコホート研究による症候性脊椎転移の発生リスクに関する検討国内学会・会議・シンポジウム等の賞
- 2017年08月 第6回Japan Association of Spine Surgeons With Ambition, Best Presenter Award, 症候性脊椎転移の発生リスクに関する前向き研究国内学会・会議・シンポジウム等の賞
- 2017年01月 Journal of Orthopaedic Research, Wiley, USA, JOR 2016 Top Reviewers, JOR 2016 Top Reviewers
- 2017年 Journal of Orthopaedic Research, JOR 2016 Top Reviewers, Journal of Orthopaedic Research国際学会・会議・シンポジウム等の賞
- 2016年03月 第45回脊椎外科を学ぶ会, 最優秀演題賞, 硬膜内髄外腫瘍に起因する水頭症により意識障害を呈した2例
- 2015年11月 The 43rd Annual Meeting, Cervical Spine Research Society, 2nd Place Clinical Research Paper Award, Predictive risk factors of cervical spine instabilities in rheumatoid arthritis: a prospective minimum 10-year multicenter cohort study
- 2015年10月 第49回日本本側弯症学会学術集会, 最優秀ポスター賞, 重度症候性側弯手術での椎弓根スクリュー刺入における電磁波センサー付きプローブの有効性
- 2014年06月 The 41st Annual Meeting, International Society for the Study of the Lumbar Spine, ISSLS Best Posters 2014, Mechanobiology of complex loading in functional spinal units: flexion/extension with combined torsion
- 2013年04月 第120回中部日本整形外科災害外科学会学術集会, 学会奨励賞, 椎間板変性では脊索由来細胞の消失を契機として細胞外基質の分解が進行する－ラット椎間板変性モデルでの検討－
- 2012年04月 第41回日本脊椎脊髄病学会学術集会, 学会奨励賞：大正富山アワード, Progression of cervical spine instabilities in rheumatoid arthritis: a prospective cohort study of outpatients over 5 years
- 2011年12月 The 39th Annual Meeting, Cervical Spine Research Society, 2nd Place Clinical Research Paper Award, Accelerated development of cervical spine instabilities in rheumatoid arthritis -a prospective minimum five-year follow-up study-
- (公社)日本整形外科学会, 2024年03月, 日本整形外科学会雑誌, 98(3) (3), S1250 - S1250, 日本語
- OBJECTIVE: To elucidate the patient characteristics and outcomes of emergency surgery for spinal metastases and identify risk factors for emergency surgery. METHODS: We prospectively analyzed 216 patients with spinal metastases who underwent palliative surgery from 2015 to 2020. The Eastern Cooperative Oncology Group performance status, Barthel index, EuroQol-5 dimension (EQ5D), and neurological function were assessed at surgery and at 1, 3, and 6 months postoperatively. Multivariate analysis was performed to identify risk factors for emergency surgery. RESULTS: In total, 146 patients underwent nonemergency surgery and 70 patients underwent emergency surgery within 48 hours of diagnosis of a surgical indication. After propensity score matching, we compared 61 patients each who underwent nonemergency and emergency surgery. Regardless of matching, the median performance status and the mean Barthel index and EQ5D score showed a tendency toward worse outcomes in the emergency than nonemergency group both preoperatively and 1 month postoperatively, although the surgery greatly improved these values in both groups. The median survival time tended to be shorter in the emergency than nonemergency group. The multivariate analysis showed that lesions located at T3-10 (p = 0.002; odds ratio [OR], 2.92; 95% confidence interval [CI], 1.48-5.75) and Frankel grades A-C (p < 0.001; OR, 4.91; 95% CI, 2.45-9.86) were independent risk factors for emergency surgery. CONCLUSION: Among patients with spinal metastases, preoperative and postoperative subjective health values and postoperative survival are poorer in emergency than nonemergency surgery. Close attention to patients with T3-10 metastases is required to avoid poor outcomes after emergency surgery.2024年03月, Neurospine, 21(1) (1), 314 - 327, 英語, 国際誌研究論文（学術雑誌）
- Background and Objectives: Bone metastasis cancer boards (BMCBs) focusing on the management of bone metastases have been gathering much attention. However, the association of BMCBs with spinal surgery in patients with spinal metastases remains unclear. In this retrospective single-center observational study, we aimed to clarify the effect of a BMCB on spinal metastasis treatment. Materials and Methods: We reviewed consecutive cases of posterior decompression and/or instrumentation surgery for metastatic spinal tumors from 2008 to 2019. The BMCB involved a team of specialists in orthopedics, rehabilitation medicine, radiation oncology, radiology, palliative supportive care, oncology, and hematology. We compared demographics, eastern cooperative oncology group performance status (ECOGPS), Barthel index (BI), number of overall versus emergency surgeries, and primary tumors between patients before (2008-2012) and after (2013-2019) BMCB establishment. Results: A total of 226 patients including 33 patients before BMCB started were enrolled; lung cancer was the most common primary tumor. After BMCB establishment, the mean patient age was 5 years older (p = 0.028), the mean operating time was 34 min shorter (p = 0.025), the mean hospital stay was 34.5 days shorter (p < 0.001), and the mean BI before surgery was 12 points higher (p = 0.049) than before. Moreover, the mean number of surgeries per year increased more than fourfold to 27.6 per year (p < 0.01) and emergency surgery rates decreased from 48.5% to 29.0% (p = 0.041). Patients with an unknown primary tumor before surgery decreased from 24.2% to 9.3% (p = 0.033). Postoperative deterioration rates from 1 to 6 months after surgery of ECOGPS and BI after BMCB started were lower than before (p = 0.045 and p = 0.027, respectively). Conclusion: The BMCB decreased the emergency surgery and unknown primary tumor rate despite an increase in the overall number of spinal surgeries. The BMCB also contributed to shorter operation times, shorter hospital stays, and lower postoperative deterioration rates of ECOGPS and BI.2023年11月, Medicina (Kaunas, Lithuania), 59(12) (12), 英語, 国際誌研究論文（学術雑誌）
- It is our pleasure to announce the publication of the Special Issue "Regeneration for Spinal Diseases 3.0" in the International Journal of Molecular Sciences (ISSN 1422-0067) [...].2023年11月, International journal of molecular sciences, 24(22) (22), 英語, 国際誌
- (株)先端医学社, 2023年08月, Loco Cure, 9(3) (3), 243 - 248, 日本語
- The number of advanced-age patients with spinal metastases is rising. This study was performed to clarify the characteristics and surgical outcomes of spinal metastases in advanced-age patients. We prospectively analyzed 216 patients with spinal metastases from 2015 to 2020 and divided them into three age groups: <70 years (n = 119), 70-79 years (n = 73), and ≥80 years (n = 24). Although there were no significant intergroup differences in preoperative characteristics and surgery-related factors except for age, patients aged ≥80 years tended to have a worse performance status (PS), Barthel index, and EuroQol-5 dimension (EQ-5D) before and after surgery than the other two groups. Although the median PS, mean Barthel index and mean EQ-5D greatly improved postoperatively in each group, the median PS and mean Barthel index at 6 months and the mean EQ-5D at 1 month postoperatively were significantly poorer in the ≥80-year group than the 70-79-year group. The rates of postoperative complications and re-deterioration of the EQ-5D were significantly higher in the oldest group than in the other two groups. Although surgery for spinal metastases improved the PS, Barthel index, and EQ-5D regardless of age, clinicians should be aware of the poorer outcomes and higher complication rates in advanced-age patients.2023年07月, Journal of clinical medicine, 12(14) (14), 英語, 国際誌研究論文（学術雑誌）
- BACKGROUND: Degenerative disc disease, a major cause of low back pain and associated neurological symptoms, is a global health problem with the high morbidity, workforce loss, and socioeconomic burden. The present surgical strategy of disc resection and/or spinal fusion results in the functional loss of load, shock absorption, and movement; therefore, the development of new biological therapies is demanded. This achievement requires the understanding of intervertebral disc cell fate during aging and degeneration. METHODS: Literature review was performed to clarify the current concepts and future perspectives of disc cell fate, focused on apoptosis, senescence, and autophagy. RESULTS: The intervertebral disc has a complex structure with the nucleus pulposus (NP), annulus fibrosus (AF), and cartilage endplates. While the AF arises from the mesenchyme, the NP originates from the notochord. Human disc NP notochordal phenotype disappears in adolescence, accompanied with cell death induction and chondrocyte proliferation. Discs morphologically and biochemically degenerate from early childhood as well, thereby suggesting a possible involvement of cell fate including age-related phenotypic changes in the disease process. As the disc is the largest avascular organ in the body, nutrient deprivation is a suspected contributor to degeneration. During aging and degeneration, disc cells undergo senescence, irreversible growth arrest, producing proinflammatory cytokines and matrix-degradative enzymes. Excessive stress ultimately leads to programmed cell death including apoptosis, necroptosis, pyroptosis, and ferroptosis. Autophagy, the intracellular degradation and recycling system, plays a role in maintaining cell homeostasis. While the incidence of apoptosis and senescence increases with age and degeneration severity, autophagy can be activated earlier, in response to limited nutrition and inflammation, but impaired in aged, degenerated discs. The phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) is a signal integrator to determine disc cell fate. CONCLUSIONS: Cell fate and microenvironmental regulation by modulating PI3K/Akt/mTOR signaling is a potential biological treatment for degenerative disc disease.2023年06月, North American Spine Society journal, 14, 100210 - 100210, 英語, 国際誌研究論文（学術雑誌）
- (公社)日本整形外科学会, 2023年06月, 日本整形外科学会雑誌, 97(6) (6), S1352 - S1352, 日本語
- INTRODUCTION: Patients with nonidiopathic scoliosis often have a high risk associated with general anesthesia because of cardiac or pulmonary dysfunction secondary to underlying diseases. Base excess has been reported as a predictor in the management of trauma and cancer, although not yet in scoliosis. This study was performed to clarify the surgical outcomes and the association of perioperative complications with base excess in patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia. METHODS: Patients with nonidiopathic scoliosis who were referred to our institution from 2009 to 2020 because of their high risk associated with general anesthesia were retrospectively enrolled. High-risk factors for anesthesia were determined by a senior anesthesiologist and categorized into circulatory or pulmonary dysfunction. Perioperative complications were analyzed using the Clavien-Dindo classification; severe complications were defined as grade ≥III. We investigated high-risk factors for anesthesia, underlying diseases, preoperative and postoperative Cobb angle, surgery-related factors, base excess, and postoperative management. These variables were statistically compared between patients with and without complications. RESULTS: Thirty-six patients (mean age, 17.9 years old; range, 11-40 years old) were enrolled (two patients declined surgery). High-risk factors were circulatory dysfunction in 16 patients and pulmonary dysfunction in 20 patients. The mean Cobb angle improved from 85.1° (36°-128°) preoperatively to 43.6° (9°-83°) postoperatively. Three intraoperative complications and 23 postoperative complications occurred in 20 (55.6%) patients. Severe complications occurred in 10 (27.8%) patients. All patients underwent postoperative intensive care unit management after posterior all-screw construction. A large preoperative Cobb angle (p=0.021) and base excess outliers (>3 or <-3 mEq/L) (p=0.005) were significant risk factors for complications. CONCLUSIONS: Patients with nonidiopathic scoliosis who have a high risk associated with general anesthesia have a higher complication rate. Preoperative large deformity and base excess (>3 or <-3 mEq/L) could be predictors of complications.2023年05月, Spine surgery and related research, 7(3) (3), 268 - 275, 英語, 国内誌研究論文（学術雑誌）
- Adiponectin, a hormone secreted by adipocytes, has anti-inflammatory effects and is involved in various physiological and pathological processes such as obesity, inflammatory diseases, and cartilage diseases. However, the function of adiponectin in intervertebral disc (IVD) degeneration is not well understood. This study aimed to elucidate the effects of AdipoRon, an agonist of adiponectin receptor, on human IVD nucleus pulposus (NP) cells, using a three-dimensional in vitro culturing system. This study also aimed to elucidate the effects of AdipoRon on rat tail IVD tissues using an in vivo puncture-induced IVD degeneration model. Analysis using quantitative polymerase chain reaction demonstrated the downregulation of gene expression of proinflammatory and catabolic factors by interleukin (IL)-1β (10 ng/mL) in human IVD NP cells treated with AdipoRon (2 μM). Furthermore, western blotting showed AdipoRon-induced suppression of p65 phosphorylation (p < 0.01) under IL-1β stimulation in the adenosine monophosphate-activated protein kinase (AMPK) pathway. Intradiscal administration of AdipoRon was effective in alleviating the radiologic height loss induced by annular puncture of rat tail IVD, histomorphological degeneration, production of extracellular matrix catabolic factors, and expression of proinflammatory cytokines. Therefore, AdipoRon could be a new therapeutic candidate for alleviating the early stage of IVD degeneration.2023年05月, International journal of molecular sciences, 24(10) (10), 英語, 国際誌研究論文（学術雑誌）
- 2023年03月, Am J Case Rep, 24, e939368, 英語Separation Surgery and Postoperative Intensity-Modulated Radiation Therapy for a High-Grade Myxofibrosarcoma Involving the Spine: A Case Report[査読有り]研究論文（学術雑誌）
- (公社)日本整形外科学会, 2023年03月, 日本整形外科学会雑誌, 97(2) (2), S289 - S289, 日本語
- 2023年02月, Cancers (Basel), 15(4) (4), 1251, 英語The Identification of Risk Factors for Symptomatic Spinal Metastasis Onset: A Prospective Cohort Study of 128 Asymptomatic Spinal Metastasis Patients[査読有り]研究論文（学術雑誌）
- BACKGROUND: Primary spinal osteosarcoma is a rare and intractable disease. Although en bloc resection is favorable for longer survival, it is not always achievable. Separation surgery, a partial resection with circumferential separation to safely deliver high-dose irradiation including intensity-modulated radiation therapy (IMRT), has been recently indicated for patients with spinal cord compression secondary to solid tumor metastases. However, little evidence regarding this combination approach to spinal osteosarcoma exists. CASE PRESENTATION: We report a 55-year-old male patient with a T1 tumor who underwent urgent decompression surgery for epidural spinal cord compression. Pathological findings revealed primary osteosarcoma. Separation surgery, IMRT, and adjuvant chemotherapy were applied to reduce the symptoms of epidural spinal cord compression. The patient was alive without local recurrence at the 5-year follow-up. CONCLUSIONS: Separation surgery with IMRT can be a relatively safe and effective treatment option in patients with osteosarcoma adjacent to spinal cord when en-bloc resection is challenging.2023年, Clinical medicine insights. Case reports, 16, 11795476231171891 - 11795476231171891, 英語, 国際誌
- 2022年12月, Medicine (Baltimore), 101(52) (52), e32330, 英語Effect of low body mass index on clinical recovery after fusion surgery for osteoporotic vertebral fracture: A retrospective, multicenter study of 237 cases[査読有り]研究論文（学術雑誌）
- 2022年12月, Medicina (Kaunas), 59(1) (1), 22, 英語Influence of the Preoperative Duration of Symptoms on Patients' Clinical Outcomes after Minimally Invasive Surgery-Transforaminal Lumbar Interbody Fusion for Degenerative Lumbar Spinal Diseases[査読有り]研究論文（学術雑誌）
- 2022年10月, J Clin Med, 11(21) (21), 6227, 英語Survival Rate after Palliative Surgery Alone for Symptomatic Spinal Metastases: A Prospective Cohort Study[査読有り]研究論文（学術雑誌）
- 2022年08月, Int J Mol Sci, 23(17) (17), 9710, 英語Concepts of Regeneration for Spinal Diseases in 2022[査読有り][招待有り]研究論文（学術雑誌）
- Growth differentiation factors (GDFs) regulate homeostasis by amplifying extracellular matrix anabolism and inhibiting pro-inflammatory cytokine production in the intervertebral disc (IVD). The aim of this study was to elucidate the effects of GDF-6 on human IVD nucleus pulposus (NP) cells using a three-dimensional culturing system in vitro and on rat tail IVD tissues using a puncture model in vivo. In vitro, Western blotting showed decreased GDF-6 expression with age and degeneration severity in surgically collected human IVD tissues (n = 12). Then, in moderately degenerated human IVD NP cells treated with GDF-6 (100 ng/mL), immunofluorescence demonstrated an increased expression of matrix components including aggrecan and type II collagen. Quantitative polymerase chain reaction analysis also presented GDF-6-induced downregulation of pro-inflammatory tumor necrosis factor (TNF)-α (p = 0.014) and interleukin (IL)-6 (p = 0.016) gene expression stimulated by IL-1β (10 ng/mL). Furthermore, in the mitogen-activated protein kinase pathway, Western blotting displayed GDF-6-induced suppression of p38 phosphorylation (p = 0.041) under IL-1β stimulation. In vivo, intradiscal co-administration of GDF-6 and atelocollagen was effective in alleviating rat tail IVD annular puncture-induced radiologic height loss (p = 0.005), histomorphological degeneration (p < 0.001), matrix metabolism (aggrecan, p < 0.001; type II collagen, p = 0.001), and pro-inflammatory cytokine production (TNF-α, p < 0.001; IL-6, p < 0.001). Consequently, GDF-6 could be a therapeutic growth factor for degenerative IVD disease.2022年03月, Cells, 11(7) (7), 英語, 国際誌研究論文（学術雑誌）
- 2022年03月, Osteoarthritis Cartilage, 30(3) (3), 481 - 493, 英語Involvement of autophagy in the maintenance of rat intervertebral disc homeostasis: an in-vitro and in-vivo RNA interference study of Atg5[査読有り]研究論文（学術雑誌）
- An electrical conductivity-measuring device (ECD) has recently been developed to support pedicle screw placement. However, no evidence exists regarding its efficacy for syndromic/neuromuscular scoliosis with extremely difficult screwing. We retrospectively reviewed 2010-2016 medical records of 21 consecutive syndromic/neuromuscular scoliosis patients undergoing free-hand segmental fixation surgery at our institution and compared the pedicle screw insertion accuracy and safety between 10 with a conventional non-ECD probe (2010-2013) and 11 with an ECD probe (2014-2016). We analyzed preoperative pedicle shape and postoperative screw placement in computed tomography. There were no significant differences between ECD and non-ECD groups in demographic, clinical, and treatment characteristics including scoliosis severity and pedicle diameter. The abandonment rate due to liquorrhea or perforation was lower in ECD (12.3%) than in non-ECD (26.7%) (p < 0.01). Acceptable insertion without perforation or <2-mm lateral/cranial position was more frequent in ECD (67.1%) than in non-ECD (56.9%) (p = 0.02). Critical ≥5-mm medial/caudal malposition was not seen in ECD (0.0%) but in non-ECD (2.4%) (p = 0.02). The perforation distance was shorter in ECD (2.2 ± 1.1 mm) than in non-ECD (2.6 ± 1.7 mm) (p = 0.01). Results involve small sample size, selection, performance, and learning curve biases; nevertheless, ECD could be useful for more accurate and safer pedicle screw placement in severe syndromic/neuromuscular scoliosis.2022年01月, Journal of clinical medicine, 11(2) (2), 英語, 国際誌研究論文（学術雑誌）
- Objective: To clarify the complications of posterior fusion for atlantoaxial instability (AAI) in children with Down syndrome and to discuss the significance of surgical intervention.Methods: Twenty pediatric patients with Down syndrome underwent posterior fusion for AAI between February 2000 and September 2018 (age, 6.1 ± 1.9 years). C1–2 or C1–3 fusion and occipitocervical fusion were performed in 14 and 6 patients, respectively. The past medical history, operation time, estimated blood loss (EBL), duration of Halo vest immobilization, postoperative follow-up period, and intra- and perioperative complications were examined.Results: The operation time was 257.9 ± 55.6 minutes, and the EBL was 101.6 ± 77.9 mL. Complications related to the operation occurred in 6 patients (30.0%). They included 1 major complication (5.0%): hydrocephalus at 3 months postoperatively, possibly related to an intraoperative dural tear. Other surgery-related complications included 3 cases of superficial infections, 1 case of bone graft donor site deep infection, 1 case of C2 pedicle fracture, 1 case of Halo ring dislocation, 1 case of pseudoarthrosis that required revision surgery, and 1 case of temporary neurological deficit after Halo removal at 2 months postoperatively. Complications unrelated to the operation included 2 cases of respiratory infections and 1 case of implant loosening due to a fall at 9 months postoperatively.Conclusion: The complication rate of upper cervical fusion in patients with Down syndrome remained high; however, major complications decreased substantially. Improved intra- and perioperative management facilitates successful surgical intervention for upper cervical instability in pediatric patients with Down syndrome.The Korean Spinal Neurosurgery Society, 2021年12月, Neurospine, 18(4) (4), 778 - 785研究論文（学術雑誌）
- 2021年12月, Neurospine, 18(4) (4), 903 - 913, 英語Upper Cervical Compression Myelopathy Caused by the Retro-Odontoid Pseudotumor With Degenerative Osteoarthritis and Calcium Pyrophosphate Dihydrate Disease: A Case Report and Literature Review[査読有り]研究論文（学術雑誌）
- (株)医学書院, 2021年10月, 臨床整形外科, 56(10) (10), 1231 - 1237, 日本語
- 中部日本整形外科災害外科学会, 2021年09月, 中部日本整形外科災害外科学会雑誌, 64(5) (5), 615 - 616, 日本語
- It is our pleasure to announce the publication of the Special Issue "Regeneration for Spinal Diseases" in the International Journal of Molecular Sciences (IJMS, ISSN 1422-0067) [...].2021年08月, International journal of molecular sciences, 22(16) (16), 英語, 国際誌研究論文（学術雑誌）
- 2021年08月, 週間医学のあゆみ, 27(1) (1), 4 - 9, 日本語慢性腰痛の発生機序，現在の診療指針，そして将来の治療戦略[招待有り]研究論文（学術雑誌）
- BACKGROUND: Few studies have addressed the impact of palliative surgery for cervical spine metastasis on patients' performance status (PS) and quality of life (QOL). We investigated the surgical outcomes of patients with cervical spine metastasis and the risk factors for a poor outcome with a focus on the PS and QOL. METHODS: We prospectively analyzed patients with cervical spine metastasis who underwent palliative surgery from 2013 to 2018. The Eastern Cooperative Oncology Group PS (ECOGPS) and EuroQol 5-Dimension (EQ5D) score were assessed at study enrollment and 1, 3, and 6 months postoperatively. Neurological function was evaluated with Frankel grading. Univariate and multivariate analyses were performed to identify the risk factors for a poor surgical outcome, defined as no improvement or deterioration after improvement of the ECOGPS or EQ5D score within 3 months. RESULTS: Forty-six patients (mean age, 67.5 ± 11.7 years) were enrolled. Twelve postoperative complications occurred in 11 (23.9%) patients. The median ECOGPS improved from PS3 at study enrolment to PS2 at 1 month and PS1 at 3 and 6 months postoperatively. The mean EQ5D score improved from 0.085 ± 0.487 at study enrolment to 0.658 ± 0.356 at 1 month and 0.753 ± 0.312 at 3 months. A poor outcome was observed in 18 (39.1%) patients. The univariate analysis showed that variables with a P value of < 0.10 were sex (male), the revised Tokuhashi score, the new Katagiri score, the level of the main lesion, and the Frankel grade at baseline. The multivariate analysis identified the level of the main lesion (cervicothoracic junction) as the significant risk factor (odds ratio, 5.00; P = 0.025). CONCLUSIONS: Palliative surgery for cervical spine metastasis improved the PS and QOL, but a cervicothoracic junction lesion could be a risk factor for a poor outcome.2021年07月, Journal of orthopaedic surgery and research, 16(1) (1), 423 - 423, 英語, 国際誌研究論文（学術雑誌）
- INTRODUCTION: Corrective surgery for spinal deformity associated with osteogenesis imperfecta (OI) is challenging due to the severe and rigid deformity combined with extreme bone fragility. However, surgical outcomes still remain unclear. In addition, the applicability of pedicle screws (PSs) to the tiny and fragile vertebrae in patients with OI is poorly understood. This study evaluated the surgical outcome, and the accuracy and safety of PS placement in patients with OI. METHODS: Twenty-five patients with OI were included in this study. Mean age was 21.0±9.3 (10 to 49) years. Mean follow-up was 5.8±2.0 years. The Sillence classification showed 16 patients had the mildest type I, 1 patient had moderate type IV, and 8 patients had the most severe type III. Fifteen patients underwent anterior release followed by posterior fusion, and 10 patients underwent only posterior fusion. The accuracy of PS placement was evaluated with postoperative computed tomography. RESULTS: Scoliosis was corrected from 95.6 to 65.8 degrees after surgery (correction rate 32.5%) and 68.1 degrees at final follow-up (both, P<0.01). Space available for the lung was improved from 76.3% to 84.9% (P<0.05). No implant dislodgement occurred after surgery. A total of 290 screws were placed, of which 213 screws (73.4%) were placed completely. However, 30 screws (10.3%) penetrated >2 mm. In particular, rates of >2 mm penetration was much higher in type III than type I and IV (27.8% vs. 3.0%; P<0.01). Complications related to spinal surgery included 2 transient neurological disturbances. CONCLUSIONS: PSs were applicable to spinal fusion surgery in patients with OI. However special care should be taken in placing PSs because of the weakness of the pedicle cortex, which was easily penetrated especially in Sillence type III. LEVEL OF EVIDENCE: Level IV.2021年07月, Journal of pediatric orthopedics, 41(6) (6), 368 - 373, 英語, 国際誌研究論文（学術雑誌）
- (公社)日本整形外科学会, 2021年06月, 日本整形外科学会雑誌, 95(6) (6), S1240 - S1240, 日本語
- 2021年06月, J Spine Res, 12(6) (6), 898 - 902, 日本語胸腰椎後方固定術後の近位隣接椎間障害(PJF)として椎弓根スクリューの脊柱管内逸脱により脊髄症を発症した1例[査読有り]研究論文（学術雑誌）
- Background: The rabbit lumbar spine is a commonly utilized model for studying intervertebral disc degeneration and for the pre-clinical evaluation of regenerative therapies. Histopathology is the foundation for which alterations to disc morphology and cellularity with degeneration, or following repair or treatment are assessed. Despite this, no standardized histology grading scale has yet been established for the spine field for any of the frequently utilized animal models. Aims: The purpose of this study was to establish a new standardized scoring system to assess disc degeneration and regeneration in the rabbit model. Materials and Methods: The scoring system was formulated following a review of the literature and a survey of spine researchers. Validation of the scoring system was carried out using images provided by 4 independent laboratories, which were graded by 12 independent graders of varying experience levels. Reliability testing was performed via the computation of intra-class correlation coefficients (ICC) for each category and the total score. The scoring system was then further refined based on the results of the ICC analysis and discussions amongst the authors. Results: The final general scoring system involves scoring 7 features (nucleus pulposus shape, area, cellularity and matrix condensation, annulus fibrosus/nucleus pulposus border appearance, annulus fibrosus morphology, and endplate sclerosis/thickening) on a 0 (healthy) to 2 (severe degeneration) scale. ICCs demonstrated overall moderate to good agreement across graders. An addendum to the main scoring system is also included for use in studies evaluating regenerative therapeutics, which involves scoring cell cloning and morphology within the nucleus pulposus and inner annulus fibrosus. Discussion: Overall, this new scoring system provides an avenue to improve standardization, allow a more accurate comparison between labs and more robust evaluation of pathophysiology and regenerative treatments across the field. Conclusion: This study developed a histopathology scoring system for degeneration and regeneration in the rabbit model based on reported practice in the literature, a survey of spine researchers, and validation testing.2021年06月, JOR spine, 4(2) (2), e1147, 英語, 国際誌研究論文（学術雑誌）
- Background: Rats are a widely accepted preclinical model for evaluating intervertebral disc (IVD) degeneration and regeneration. IVD morphology is commonly assessed using histology, which forms the foundation for quantifying the state of IVD degeneration. IVD degeneration severity is evaluated using different grading systems that focus on distinct degenerative features. A standard grading system would facilitate more accurate comparison across laboratories and more robust comparisons of different models and interventions. Aims: This study aimed to develop a histology grading system to quantify IVD degeneration for different rat models. Materials & Methods: This study involved a literature review, a survey of experts in the field, and a validation study using 25 slides that were scored by 15 graders from different international institutes to determine inter- and intra-rater reliability. Results: A new IVD degeneration grading system was established and it consists of eight significant degenerative features, including nucleus pulposus (NP) shape, NP area, NP cell number, NP cell morphology, annulus fibrosus (AF) lamellar organization, AF tears/fissures/disruptions, NP-AF border appearance, as well as endplate disruptions/microfractures and osteophyte/ossification. The validation study indicated this system was easily adopted, and able to discern different severities of degenerative changes from different rat IVD degeneration models with high reproducibility for both experienced and inexperienced graders. In addition, a widely-accepted protocol for histological preparation of rat IVD samples based on the survey findings include paraffin embedding, sagittal orientation, section thickness < 10 μm, and staining using H&E and/or SO/FG to facilitate comparison across laboratories. Conclusion: The proposed histological preparation protocol and grading system provide a platform for more precise comparisons and more robust evaluation of rat IVD degeneration models and interventions across laboratories.2021年06月, JOR spine, 4(2) (2), e1150, 英語, 国際誌研究論文（学術雑誌）
- The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (n = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (n = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (n = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis.2021年05月, International journal of molecular sciences, 22(11) (11), 英語, 国際誌研究論文（学術雑誌）
- The intervertebral disc is the largest avascular organ. Autophagy is an important cell survival mechanism by self-digestion and recycling damaged components under stress, primarily nutrient deprivation. Resident cells would utilize autophagy to cope with the harsh disc environment. Our objective was to elucidate the roles of human disc cellular autophagy. In human disc cells, serum deprivation and pro-inflammatory interleukin-1β (IL-1β) stimulation increased autophagy marker microtubule-associated protein 1 light chain 3 (LC3)-II and decreased autophagy substrate p62/sequestosome 1 (p62/SQSTM1), indicating enhanced autophagy. Then, RNA interference (RNAi) of autophagy-related gene 5 (ATG5), essential for autophagy, showed decreases in ATG5 protein (26.8%-27.4%, p < 0.0001), which suppressed early-stage autophagy with decreased LC3-II and increased p62/SQSTM1. Cell viability was maintained by ATG5 RNAi in serum-supplemented media (95.5%, p = 0.28) but reduced in serum-free media (80.4%, p = 0.0013) with IL-1β (69.9%, p = 0.0008). Moreover, ATG5 RNAi accelerated IL-1β-induced changes in apoptosis and senescence. Meanwhile, ATG5 RNAi unaffected IL-1β-induced catabolic matrix metalloproteinase release, down-regulated anabolic gene expression, and mitogen-activated protein kinase pathway activation. Lysosomotropic chloroquine supplementation presented late-stage autophagy inhibition with apoptosis and senescence induction, while catabolic enzyme production was modest. Disc-tissue analysis detected age-related changes in ATG5, LC3-II, and p62/SQSTM1. In summary, autophagy protects against human disc cellular apoptosis and senescence rather than extracellular matrix catabolism.2021年04月, International journal of molecular sciences, 22(8) (8), 英語, 国際誌研究論文（学術雑誌）
- Management of bone metastasis is becoming increasingly important. Thus, local and systemic treatment options have been developed for control. Although systemic administration of anticancer agents is effective for bone metastasis, it is often stopped because of poor general conditions or side effects. Therefore, it is highly desirable to develop a more effective and safer local treatment for bone metastasis. The purpose of the current study was to investigate the antitumor effects and safety of gelatin hydrogel microspheres incorporating cisplatin (GM-CDDP), which we developed as a sustained release system without harmful substances. First, we assessed GM-CDDP for its in vitro degradability and potential for sustained release. Second, in vivo antitumor and side effects were evaluated using a murine bone metastasis model of MDA-MB-231 human breast cancer cells incorporating GFP. In vitro, initial bursts were observed within 2 h and CDDP was released gradually with gelatin hydrogel degradation, which reached 100% at 48 h. In vivo, local administration of GM-CDDP (2 mg/kg) significantly suppressed tumor growth and bone osteolysis compared with the control, and local and systemic administration of free CDDP (2 mg/kg; p < 0.05). Local administration of GM-CDDP significantly reduced loss of body weight and elevation of blood urea nitrogen compared with the systemic administration of free CDDP (p < .05). The current study suggests that local administration of GM-CDDP achieves higher antitumor effects with a potential for lesser side effects compared with local or systemic administration of free CDDP.2021年03月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 39(3) (3), 525 - 535, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- AIMS: With recent progress in cancer treatment, the number of advanced-age patients with spinal metastases has been increasing. It is important to clarify the influence of advanced age on outcomes following surgery for spinal metastases, especially with a focus on subjective health state values. METHODS: We prospectively analyzed 101 patients with spinal metastases who underwent palliative surgery from 2013 to 2016. These patients were divided into two groups based on age (< 70 years and ≥ 70 years). The Eastern Cooperative Oncology Group (ECOG) performance status (PS), Barthel index (BI), and EuroQol-5 dimension (EQ-5D) score were assessed at study enrolment and at one, three, and six months after surgery. The survival times and complications were also collected. RESULTS: In total, 65 patients were aged < 70 years (mean 59.6 years; 32 to 69) and 36 patients were aged ≥ 70 years (mean 75.9 years; 70 to 90). In both groups, the PS improved from PS3 to PS1 by spine surgery, the mean BI improved from < 60 to > 80 points, and the mean EQ-5D score improved from 0.0 to > 0.7 points. However, no significant differences were found in the improvement rates and values of the PS, BI, and EQ-5D score at any time points between the two groups. The PS, BI, and EQ-5D score improved throughout the follow-up period in approximately 90% of patients in each group. However, the improved PS, BI, and EQ-5D scores subsequently deteriorated in some patients, and the redeterioration rate of the EQ-5D was significantly higher in patients aged ≥ 70 than < 70 years (p = 0.027). CONCLUSION: Palliative surgery for spinal metastases improved the PS, activities of daily living, and quality of life, regardless of age. However, clinicians should be aware of the higher risk of redeterioration of the quality of life in advanced-age patients. Cite this article: Bone Joint J 2020;102-B(12):1709-1716.2020年12月, The bone & joint journal, 102-B(12) (12), 1709 - 1716, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- The loss of nucleus pulposus (NP) notochordal cells is one of the key initial hallmarks of age-related intervertebral disc degeneration. Although the transmembrane mechanoreceptor integrin α5β1 is important in the process of disc degeneration, the relationship between integrin α5β1 and notochordal cell disappearance remains unclear. The purpose of this study was to elucidate the role of integrin α5β1 in the homeostasis of notochordal cells using an ex-vivo dynamic loading culture system that we developed. Rat tail functional spinal units (n = 80 from 40 rats) were cultured under unloading or 1.3-MPa, 1.0-Hz dynamic compressive loading for 48 or 144 h with or without an integrin α5β1 inhibitor. Disc histomorphology, cell viability, apoptosis, senescence, and phenotypic expression were investigated. Consequently, histological degenerative disc changes with decreased cell viability and increased cell apoptosis and senescence were observed with an extended loading duration. Immunofluorescence revealed that the expression of notochordal cell markers, CD24 and brachyury, and chondrocyte markers, collagen type II and SRY-box 9, declined with loading. In particular, reduction in notochordal cell marker expression was more dramatic than that in chondrocyte marker expression. Apoptotic terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity was also higher in brachyury-positive notochordal cells. Furthermore, all these changes were delayed by inhibiting integrin α5β1. Findings of our dynamic loading regimen with a relatively high pressure suggest reproducibility of the cellularity and phenotypic disappearance of NP notochordal cells during adolescence, the susceptibility of notochordal cells to mechanical stimuli partially through the integrin α5β1 pathway, and future potential treatment of integrin regulation for intervertebral disc disease.2020年10月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 39(9) (9), 1933 - 1944, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)中部日本整形外科災害外科学会, 2020年10月, 中部日本整形外科災害外科学会雑誌, 63(秋季学会) (秋季学会), 15 - 15, 日本語転移性骨腫瘍の治療戦略 脊椎転移手術の術後創離開に関する傾向と対策
- BACKGROUND: Vertebroplasty with posterior spinal fusion (VP + PSF) is one of the most widely accepted surgical techniques for treating osteoporotic vertebral collapse (OVC). Nevertheless, the effect of the extent of fusion on surgical outcomes remains to be established. This study aimed to evaluate the surgical outcomes of short- versus long-segment VP + PSF for OVC with neurological impairment in thoracolumbar spine. METHODS: We retrospectively collected data from 133 patients (median age, 77 years; 42 men and 91 women) from 27 university hospitals and their affiliated hospitals. We divided patients into two groups: a short-segment fusion group (S group) with 2- or 3-segment fusion (87 patients) and a long-segment fusion group (L group) with 4- through 6-segment fusion (46 patients). Surgical invasion, clinical outcomes, local kyphosis angle (LKA), and complications were evaluated. RESULTS: No significant differences between the two groups were observed in terms of neurological recovery, pain scale scores, and complications. Surgical time was shorter and blood loss was less in the S group, whereas LKA at the final follow-up and correction loss were superior in the L group. CONCLUSION: Although less invasiveness and validity of pain and neurological relief are secured by short-segment VP + PSF, surgeons should be cautious regarding correction loss.2020年08月, BMC musculoskeletal disorders, 21(1) (1), 513 - 513, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公社)日本整形外科学会, 2020年07月, 日本整形外科学会雑誌, 94(6) (6), S1528 - S1528, 日本語脊椎腫瘍に対するseparation surgeryとIMRTの併用による治療成績 7例のケースシリーズ
- (公社)日本リハビリテーション医学会, 2020年07月, The Japanese Journal of Rehabilitation Medicine, 57(特別号) (特別号), 3 - 2, 日本語頸椎転移患者の手術成績と成績不良因子の検討 PS、QOLの推移から
- 2020年07月, Bone Joint Nerve, 10(3) (3)がんロコモ:がん診療のニューフロンティア Part7 オートメーションのニューフロンティア(がんロコモ診療のオートメーション化)脊髄圧迫の対応[査読有り]
- BACKGROUND: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures. METHODS: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced. RESULTS: A total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP. CONCLUSIONS: The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.2020年07月, BMC musculoskeletal disorders, 21(1) (1), 420 - 420, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: Osteoporotic vertebral fracture (OVF) with nonunion or neurological deficit may be a candidate for surgical treatment. However, some patients do not show improvement as expected. Therefore, we conducted a nationwide multicenter study to determine the predictors for postoperative poor activity of daily living (ADL) in patients with OVF. METHODS: We retrospectively reviewed the case histories of 309 patients with OVF who underwent surgery. To determine the factors predicting postoperative poor ADL, uni- and multivariate statistical analyses were performed. RESULTS: The frequency of poor ADL at final follow-up period was 9.1%. In univariate analysis, preoperative neurological deficit (OR, 4.1; 95% CI, 1.8-10.3; P < 0.001), perioperative complication (OR, 3.4; P = 0.006), absence of preoperative bone-modifying agent (BMA) administration (OR, 2.7; P = 0.03), and absence of postoperative recombinant human parathyroid hormone (rPTH) administration (OR, 3.9; P = 0.006) were significantly associated. In multivariate analysis, preoperative neurological deficit (OR, 4.6; P < 0.001), perioperative complication (OR, 3.4; P = 0.01), and absence of postoperative rPTH administration (OR, 3.9; P = 0.02) showed statistical significance. CONCLUSIONS: Preoperative neurological deficit, perioperative complication, and absence of postoperative rPTH administration were considered as predictors for postoperative poor ADL in patients with OVF. Neurological deficits and complications are often inevitable factors; therefore, rPTH is an important option for postoperative treatment for OVF. These slides can be retrieved under Electronic Supplementary Material.2020年07月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 29(7) (7), 1597 - 1605, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)中部日本整形外科災害外科学会, 2020年04月, 中部日本整形外科災害外科学会雑誌, 63(春季学会) (春季学会), 81 - 81, 日本語頸椎転移に対する後方手術成績と術後成績不良因子の検討
- STUDY DESIGN: Retrospective case series. OBJECTIVE: To elucidate the postoperative course of sagittal alignment in patients with congenital thoracolumbar to lumbar kyphosis or kyphoscoliosis. Acquisition of acceptable sagittal alignment is essential to treat spinal deformity. Little evidence exists regarding long-term surgical outcomes on sagittal alignment in congenital kyphosis or kyphoscoliosis. METHODS: Sixteen consecutive patients (mean age 10.5 ± 3.5 years) with congenital kyphosis or kyphoscoliosis who underwent vertebra resection and osteotomy with instrumentation by single posterior or combined anterior and posterior approach were included. Preoperative radiographs identified kyphosis in 3 patients and kyphoscoliosis in 13 patients. All patients had clinical and radiologic follow-up for > 10 years (mean 16.3 ± 4.0 years). RESULTS: Segmental kyphosis was significantly improved from 33.9° ± 20.1° to 14.9° ± 17.6° by surgery and was finally maintained at 16.8° ± 22.2° and sagittal vertical axis (SVA) of 13.1 ± 33.7 mm at preoperation and 18.3 ± 22.1 mm at postoperation significantly increased to 26.8 ± 45.7 mm during follow-up. Of the 16 patients, 5 (31%) were identified as those with SVA > 40 mm, and SVA increases > 30 mm during follow-up. In patients with sagittal malalignment, radiographs demonstrated decreased lumbar lordosis at the lower foundation from 28.8° ± 39.0° to 17.0° ± 17.6°, significant increased pelvic tilt from 25.8° ± 5.4° to 37.4° ± 7.4° during follow-up (p < 0.05), and larger residual segmental kyphosis than those in the 11 patients without sagittal malalignment with statistical significance. Of the five cases, progression of local kyphosis (one case) and sagittal decompensation, including decreased lumbar lordosis with disc degeneration (four cases), increased pelvic tilt (three cases), or proximal junctional kyphosis (two cases), were observed. CONCLUSION: Based on this > 10-year follow-up study, residual kyphosis and sagittal decompensation are revealed to be risk factors for postoperative sagittal malalignment in patients with congenital thoracolumbar to lumbar kyphosis or kyphoscoliosis. LEVEL OF EVIDENCE: Level IV, case series.2020年04月, Spine deformity, 8(2) (2), 245 - 256, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公社)日本整形外科学会, 2020年03月, 日本整形外科学会雑誌, 94(3) (3), S1096 - S1096, 日本語頸椎転移の手術成績と成績不良因子の検討
- (一社)日本脊椎脊髄病学会, 2020年03月, Journal of Spine Research, 11(3) (3), 221 - 221, 日本語転移性頸椎腫瘍に対する後方手術成績と術後成績不良因子の検討
- (一社)日本脊椎脊髄病学会, 2020年03月, Journal of Spine Research, 11(3) (3), 73 - 73, 日本語慢性腰痛症に対する薬物療法の合併症評価 肝腎機能障害を中心に 日本脊椎脊髄病学会主導多施設前向き追跡調査
- Laminoplasty using hydroxyapatite (HA) spacers is widely performed in patients with cervical myelopathy. However, spacer dislocation is a critical complication caused by bone absorption and inadequate bone conductivity, and can result in dural damage and restenosis. We thus designed a prospective cohort study to clarify the feasibility of increased porosity HA spacers for double-door laminoplasty by analyzing computed tomography (CT) images. Forty-seven patients underwent cervical laminoplasty. Two different types of CERATITE HA spacer were used, either high porosity (50%) or low porosity (35%). These HA spacers were placed in an alternating manner into the laminae in each patient. In total, 85 high-porosity (50%) HA spacers and 84 low-porosity (35%) HA spacers were implanted. At postoperative 2 weeks, 3 months, 6 months, and 1 year, CT images were obtained. In both groups, the percentage of bone-bonding boundary area of the HA spacer in contact with laminae and bone volume of the spinous process relative to the 2-week value were calculated by a 3D and 2D CT-image pixel analysis. The bone-bonding ratio was significantly higher in high-porosity (50%) than low-porosity (35%) HA spacers at 3 months and thereafter (1 year, 69.3 ± 27.8% and 49.7 ± 32.9% respectively, P < .01). The bone volume in both groups significantly decreased with time (1 year, 73.2 ± 29.8% and 69.0 ± 30.4% respectively, P < .01), indicating bone absorption. This showed no significant difference between the HA spacers (P = .15) but was higher in high-porosity (50%) than low-porosity (35%) HA spacers throughout the study period. Meanwhile, spacer breakage was found in 4.7% of high-porosity (50%) HA spacers and 1.2% of low-porosity (35%) HA spacers (P = .37). In summary, high-porosity (50%) HA spacers have the advantages of accelerated bone bonding and relatively decelerated bone absorption compared to low-porosity (35%) HA spacers; however, possibly more frequent breakage of HA spacers with a high porosity (50%) requires careful, extended postoperative follow-up.2020年03月, JOR spine, 3(1) (1), e1080, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Degenerative disc disease is a highly prevalent, global health problem that represents the primary cause of back pain and is associated with neurological disorders, including radiculopathy, myelopathy, and paralysis, resulting in worker disability and socioeconomic burdens. The intervertebral disc is the largest avascular organ in the body, and degeneration is suspected to be linked to nutritional deficiencies. Autophagy, the process through which cells self-digest and recycle damaged components, is an important cell survival mechanism under stress conditions, especially nutrient deprivation. Autophagy is negatively controlled by the mammalian target of rapamycin (mTOR) signaling pathway. mTOR is a serine/threonine kinase that detects nutrient availability to trigger the activation of cell growth and protein synthesis pathways. Thus, resident disc cells may utilize autophagy and mTOR signaling to cope with harsh low-nutrient conditions, such as low glucose, low oxygen, and low pH. We performed rabbit and human disc cell and tissue studies to elucidate the involvement and roles played by autophagy and mTOR signaling in the intervertebral disc. In vitro serum and nutrient deprivation studies resulted in decreased disc cell proliferation and metabolic activity and increased apoptosis and senescence, in addition to increased autophagy. The selective RNA interference-mediated and pharmacological inhibition of mTOR complex 1 (mTORC1) was protective against inflammation-induced disc cellular apoptosis, senescence, and extracellular matrix catabolism, through the induction of autophagy and the activation of the Akt-signaling network. Although temsirolimus, a rapamycin derivative with improved water solubility, was the most effective mTORC1 inhibitor tested, dual mTOR inhibitors, capable of blocking multiple mTOR complexes, did not rescue disc cells. In vivo, high levels of mTOR-signaling molecule expression and phosphorylation were observed in human intermediately degenerated discs and decreased with age. A mechanistic understanding of autophagy and mTOR signaling can provide a basis for the development of biological therapies to treat degenerative disc disease.2020年03月, JOR spine, 3(1) (1), e1082, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Intervertebral disc degeneration is the primary cause of back pain and associated with neurological disorders including radiculopathy, myelopathy, and paralysis. The currently available surgical treatments predominantly include the excision of pathological discs, resulting in the function loss, immobilization, and potential additional complications due to the altered biomechanics. Gene therapy approach involves gene transfer into cells, affects RNA and protein synthesis of the encoded genes in the recipient cells, and facilitates biological treatment. Relatively long-exerting therapeutic effects by gene therapy are potentially advantageous to treat slow progressive degenerative disc disease. In gene therapy, the delivery method and selection of target gene(s) are essential. Although gene therapy was first mediated by viral vectors, technological progress has enabled to apply nonviral vectors and polyplex micelles for the disc. While RNA interference successfully provides specific downregulation of multiple genes in the disc, clustered regularly interspaced short palindromic repeats (CRISPR) system has increased attention to alter the process of intervertebral disc degeneration. Then, more recent findings of our studies have suggested autophagy, the intracellular self-digestion, and recycling system under the negative regulation by the mammalian target of rapamycin (mTOR), as a gene therapy target in the disc. Here we briefly review backgrounds and applications of gene therapy for the disc, introducing strategies of autophagy and mTOR signaling modulation through selective RNA interference.2020年03月, Neurospine, 17(1) (1), 3 - 14, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Back pain is a global health problem with a high morbidity and socioeconomic burden. Intervertebral disc herniation and degeneration are its primary cause, further associated with neurological radiculopathy, myelopathy, and paralysis. The current surgical treatment is principally discectomy, resulting in the loss of spinal movement and shock absorption. Therefore, the development of disc regenerative therapies is essential. Here we show reduced disc damage by a new collagen type I-based scaffold through actinidain hydrolysis-Low Adhesive Scaffold Collagen (LASCol)-with a high 3D spheroid-forming capability, water-solubility, and biodegradability and low antigenicity. In human disc nucleus pulposus and annulus fibrosus cells surgically obtained, time-dependent spheroid formation with increased expression of phenotypic markers and matrix components was observed on LASCol but not atelocollagen (AC). In a rat tail nucleotomy model, LASCol-injected and AC-injected discs presented relatively similar radiographic and MRI damage control; however, LASCol, distinct from AC, decelerated histological disc disruption, showing collagen type I-comprising LASCol degradation, aggrecan-positive and collagen type II-positive endogenous cell migration, and M1-polarized and also M2-polarized macrophage infiltration. Reduced nucleotomy-induced disc disruption through spontaneous spheroid formation by LASCol warrants further investigations of whether it may be an effective treatment without stem cells and/or growth factors for intervertebral disc disease.2020年03月, Biomaterials, 235, 119781 - 119781, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Introduction: Osteoporotic vertebral fracture (OVF) is the most common osteoporotic fracture, and some patients require surgical intervention to improve their impaired activities of daily living with neurological deficits. However, many previous reports have focused on OVF around the thoracolumbar junction, and the surgical outcomes of lumbar OVF have not been thoroughly discussed. We aimed to investigate the surgical outcomes for lumbar OVF with a neurological deficit. Methods: Patients who underwent fusion surgery for thoracolumbar OVF with a neurological deficit were enrolled at 28 institutions. Clinical information, comorbidities, perioperative complications, Japanese Orthopaedic Association scores, visual analog scale scores, and radiographic parameters were compared between patients with lower lumbar fracture (L3-5) and those with thoracolumbar junction fracture (T10-L2). Each patient with lower lumbar fracture (L group) was matched with to patients with thoracolumbar junction fracture (T group). Results: A total 403 patients (89 males and 314 females, mean age: 73.8 ± 7.8 years, mean follow-up: 3.9 ± 1.7 years) were included in this study. Lower lumbar OVF was frequently found in patients with lower bone mineral density. After matching, mechanical failure was more frequent in the L group (L group: 64%, T group: 39%; p < 0.001). There was no difference between groups in the clinical and radiographical outcomes, although the rates of complication and revision surgery were still high in both groups. Conclusions: The surgical intervention for OVF is effective in patients with myelopathy or radiculopathy regardless of the surgical level, although further study is required to improve clinical and radiographical outcomes. Level of evidence: Level III.2020年, Spine surgery and related research, 4(3) (3), 199 - 207, 英語, 国内誌研究論文（学術雑誌）
- 2020年, Spine surgery and related research, 4(3) (3), 292 - 293, 英語, 国内誌研究論文（学術雑誌）
- BACKGROUND: A consensus on the optimal surgical procedure for thoracolumbar OVF has yet to be reached due to the previous relatively small number of case series. The study was conducted to investigate surgical outcomes for osteoporotic vertebral fracture (OVF) in the thoracolumbar spine. METHODS: In total, 315 OVF patients (mean age, 74 years; 68 men and 247 women) with neurological symptoms who underwent spinal fusion with a minimum 2-year follow-up were included. The patients were divided into 5 groups by procedure: anterior spinal fusion alone (ASF group, n = 19), anterior/posterior combined fusion (APSF group, n = 27), posterior spinal fusion alone (PSF group, n = 40), PSF with 3-column osteotomy (3CO group, n = 92), and PSF with vertebroplasty (VP + PSF group, n = 137). RESULTS: Mean operation time was longer in the APSF group (p < 0.05), and intraoperative blood loss was lower in the VP + PSF group (p < 0.05). The amount of local kyphosis correction was greater in the APSF and 3CO groups (p < 0.05). Clinical outcomes were approximately equivalent among all groups. CONCLUSION: All 5 procedures resulted in acceptable neurological outcomes and functional improvement in walking ability. Moreover, they were similar with regard to complication rates, prevalence of mechanical failure related to the instrumentation, and subsequent vertebral fracture. Individual surgical techniques can be adapted to suit patient condition or severity of OVF.2019年11月, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 24(6) (6), 1020 - 1026, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- BACKGROUND: There have been few reports on the incidence and risk factors of the complications after spinal fixation surgery for osteoporotic vertebral collapse (OVC) with neurological deficits. This study aimed to identify the incidence and risk factors of the complications after OVC surgery. METHODS: In this retrospective multicenter study, a total of 403 patients (314 women and 89 men; mean age 73.8 years) who underwent spinal fixation surgery for OVC with neurological deficits between 2005 and 2014 were enrolled. Data on patient demographics were collected, including age, sex, body mass index, smoking, steroid use, medical comorbidities, and surgical procedures. All postoperative complications that occurred within 6 weeks were recorded. Patients were classified into two groups, namely, complication group and no complication group, and risk factors for postoperative complications were investigated by univariate and multivariate analyses. RESULTS: Postoperative complications occurred in 57 patients (14.1%), and the most common complication was delirium (5.7%). In the univariate analysis, the complication group was found to be older (p = 0.039) and predominantly male (p = 0.049), with higher occurrence rate of liver disease (p = 0.001) and Parkinson's disease (p = 0.039) compared with the no-complication group. In the multivariate analysis, the significant independent risk factors were age (p = 0.021; odds ratio [OR] 1.051, 95% confidence interval [CI] 1.007-1.097), liver disease (p < 0.001; OR 8.993, 95% CI 2.882-28.065), and Parkinson's disease (p = 0.009; OR 3.636, 95% CI 1.378-9.599). CONCLUSIONS: Complications after spinal fixation surgery for OVC with neurological deficits occurred in 14.1%. Age, liver disease, and Parkinson's disease were demonstrated to be independent risk factors for postoperative complications.2019年11月, Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 24(6) (6), 985 - 990, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- Aging-related loss of adult stem cell function contributes to impaired tissue regeneration. Mice deficient in zinc metalloproteinase STE24 (Zmpste24-/-) exhibit premature age-related musculoskeletal pathologies similar to those observed in children with Hutchinson-Gilford progeria syndrome (HGPS). We have reported that muscle-derived stem/progenitor cells (MDSPCs) isolated from Zmpste24-/- mice are defective in their proliferation and differentiation capabilities in culture and during tissue regeneration. The mechanistic target of rapamycin complex 1 (mTORC1) regulates cell growth, and inhibition of the mTORC1 pathway extends the lifespan of several animal species. We therefore hypothesized that inhibition of mTORC1 signaling would rescue the differentiation defects observed in progeroid MDSPCs. MDSPCs were isolated from Zmpste24 -/- mice, and the effects of mTORC1 on MDSPC differentiation and function were examined. We found that mTORC1 signaling was increased in senescent Zmpste24-/- MDSPCs, along with impaired chondrogenic, osteogenic, and myogenic differentiation capacity versus wild-type MDSPCs. Interestingly, we observed that mTORC1 inhibition with rapamycin improved myogenic and chondrogenic differentiation and reduced levels of apoptosis and senescence in Zmpste24-/- MDSPCs. Our results demonstrate that age-related adult stem/progenitor cell dysfunction contributes to impaired regenerative capacities and that mTORC1 inhibition may represent a potential therapeutic strategy for improving differentiation capacities of senescent stem and muscle progenitor cells.2019年09月, Molecular therapy. Methods & clinical development, 14, 64 - 76, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (株)医学書院, 2019年08月, 臨床整形外科, 54(8) (8), 777 - 783, 日本語整形外科治療の費用対効果 転移性脊椎腫瘍に対する集学的治療の費用対効用[査読有り]
- OBJECTIVE: The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that integrates nutrients to execute cell growth. We hypothesized that mTOR is influential in the intervertebral disc-largest avascular, low-nutrient organ. Our objective was to identify the optimal mTOR inhibitor for treating human degenerative disc disease. DESIGN: mTOR complex 1 (mTORC1) regulates p70/ribosomal S6 kinase (p70/S6K), negatively regulates autophagy, and is controlled by Akt. Akt is controlled by phosphatidylinositol 3-kinase (PI3K) and mTOR complex 2 (mTORC2). mTORC1 inhibitors-rapamycin, temsirolimus, everolimus, and curcumin, mTORC1&mTORC2 inhibitor-INK-128, PI3K&mTOR inhibitor-NVP-BEZ235, and Akt inhibitor-MK-2206-were applied to human disc nucleus pulposus (NP) cells. mTOR signaling, autophagy, apoptosis, senescence, and matrix metabolism were evaluated. RESULTS: mTORC1 inhibitors decreased p70/S6K but increased Akt phosphorylation, promoted autophagy with light chain 3 (LC3)-II increases and p62/sequestosome 1 (p62/SQSTM1) decreases, and suppressed pro-inflammatory interleukin-1 beta (IL-1β)-induced apoptotic terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positivity (versus rapamycin, 95% confidence interval (CI) -0.431 to -0.194; temsirolimus, 95% CI -0.529 to -0.292; everolimus, 95% CI -0.477 to -0.241; curcumin, 95% CI -0.248 to -0.011) and poly (ADP-ribose) polymerase (PARP) and caspase-9 cleavage, senescent senescence-associated beta-galactosidase (SA-β-gal) positivity (versus rapamycin, 95% CI -0.437 to -0.230; temsirolimus, 95% CI -0.534 to -0.327; everolimus, 95% CI -0.485 to -0.278; curcumin, 95% CI -0.210 to -0.003) and p16/INK4A expression, and catabolic matrix metalloproteinase (MMP) release and activation. Meanwhile, dual mTOR inhibitors decreased p70/S6K and Akt phosphorylation without enhanced autophagy and suppressed apoptosis, senescence, and matrix catabolism. MK-2206 counteracted protective effects of temsirolimus. Additional disc-tissue analysis found relevance of mTOR signaling to degeneration grades. CONCLUSION: mTORC1 inhibitors-notably temsirolimus with an improved water solubility-but not dual mTOR inhibitors protect against inflammation-induced apoptosis, senescence, and matrix catabolism in human disc cells, which depends on Akt and autophagy induction.2019年06月, Osteoarthritis and cartilage, 27(6) (6), 965 - 976, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)日本脊椎脊髄病学会, 2019年05月, Journal of Spine Research, 10(5) (5), 898 - 904, 日本語脊椎転移に対する手術療法の効果と限界[査読有り]
- PURPOSE: The loss of nutrient supply is a suspected contributor of intervertebral disc degeneration. However, the extent to which low nutrition affects disc annulus fibrosus (AF) cells is unknown as nutrient deprivation has mainly been investigated in disc nucleus pulposus cells. Hence, an experimental study was designed to clarify the effects of limited nutrients on disc AF cell fate, including autophagy, the process by which cells recycle their own damaged components. METHODS: Rabbit disc AF cells were cultured in different media with varying serum concentrations under 5% oxygen. Cellular responses to changes in serum and nutrient concentrations were determined by measuring proliferation and metabolic activity. Autophagic flux in AF cells was longitudinally monitored using imaging cytometry and Western blotting for LC3, HMGB1, and p62/SQSTM1. Apoptosis (TUNEL staining and cleaved caspase-3 immunodetection) and cellular senescence (senescence-associated β-galactosidase assay and p16/INK4A immunodetection) were measured. RESULTS: Markers of apoptosis and senescence increased, while cell proliferation and metabolic activity decreased under the withdrawal of serum and of nutrients other than oxygen, confirming cellular stress. Time-dependent increases in autophagy markers, including LC3 puncta number per cell, LC3-II expression, and cytoplasmic HMGB1, were observed under conditions of reduced nutrition, while an autophagy substrate, p62/SQSTM1, decreased over time. Collectively, these findings suggest increased autophagic flux in disc AF cells under serum and nutrient deprivation. CONCLUSION: Disc AF cells exhibit distinct responses to serum and nutrient deprivation. Cellular responses include cell death and quiescence in addition to reduced proliferation and metabolic activity, as well as activation of autophagy under conditions of nutritional stress. These slides can be retrieved under Electronic Supplementary Material.2019年05月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 28(5) (5), 993 - 1004, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Introduction: Approximately 3% of osteoporotic vertebral fractures develop osteoporotic vertebral collapse (OVC) with neurological deficits, and such patients are recommended to be treated surgically. However, a proximal junctional fracture (PJFr) following surgery for OVC can be a serious concern. Therefore, the aim of this study is to identify the incidence and risk factors of PJFr following fusion surgery for OVC. Methods: This study retrospectively analyzed registry data collected from facilities belonging to the Japan Association of Spine Surgeons with Ambition (JASA) in 2016. We retrospectively analyzed 403 patients who suffered neurological deficits due to OVC below T10 and underwent corrective surgery; only those followed up for ≥2 years were included. Potential risk factors related to the PJFr and their cut-off values were calculated using multivariate logistic regression analysis and receiver operating characteristic (ROC) analysis. Results: Sixty-three patients (15.6%) suffered PJFr during the follow-up (mean 45.7 months). In multivariate analysis, the grade of osteoporosis (grade 2, 3: adjusted odds ratio (aOR) 2.92; p=0.001) and lower instrumented vertebra (LIV) level (sacrum: aOR 6.75; p=0.003) were independent factors. ROC analysis demonstrated that lumbar bone mineral density (BMD) was a predictive factor (area under curve: 0.72, p=0.035) with optimal cut-off value of 0.61 g/cm2 (sensitivity, 76.5%; specificity, 58.3%), but that of the hip was not (p=0.228). Conclusions: PJFr was found in 16% cases within 4 years after surgery; independent risk factors were severe osteoporosis and extended fusion to the sacrum. The lumbar BMD with cut-off value 0.61 g/cm2 may potentially predict PJFr. Our findings can help surgeons select perioperative adjuvant therapy, as well as a surgical strategy to prevent PJFr following surgery.2019年04月, Spine surgery and related research, 3(2) (2), 171 - 177, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- 金原出版(株), 2019年04月, 整形・災害外科, 62(5) (5), 567 - 574, 日本語【脊椎脊髄外科の最近の進歩】各種疾患に対する治療法・モダリティ 転移性脊椎腫瘍に対する集学的治療[査読有り]
- BACKGROUND: To date, there have been little published data on surgical outcomes for patients with PD with thoracolumbar OVF. We conducted a retrospective multicenter study of registry data to investigate the outcomes of fusion surgery for patients with Parkinson's disease (PD) with osteoporotic vertebral fracture (OVF) in the thoracolumbar junction. METHODS: Retrospectively registered data were collected from 27 universities and their affiliated hospitals in Japan. In total, 26 patients with PD (mean age, 76 years; 3 men and 23 women) with thoracolumbar OVF who underwent spinal fusion with a minimum of 2 years of follow-up were included (PD group). Surgical invasion, perioperative complications, radiographic sagittal alignment, mechanical failure (MF) related to instrumentation, and clinical outcomes were evaluated. A control group of 296 non-PD patients (non-PD group) matched for age, sex, distribution of surgical procedures, number of fused segments, and follow-up period were used for comparison. RESULTS: The PD group showed higher rates of perioperative complications (p < 0.01) and frequency of delirium than the non-PD group (p < 0.01). There were no significant differences in the degree of kyphosis correction, frequency of MF, visual analog scale of the symptoms, and improvement according to the Japanese Orthopaedic Association scoring system between the two groups. However, the PD group showed a higher proportion of non-ambulators and dependent ambulators with walkers at the final follow-up (p < 0.01). CONCLUSIONS: A similar surgical strategy can be applicable to patients with PD with OVF in the thoracolumbar junction. However, physicians should pay extra attention to intensive perioperative care to prevent various adverse events and implement a rehabilitation regimen to regain walking ability.2019年03月, BMC musculoskeletal disorders, 20(1) (1), 103 - 103, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Introduction: The prevalence of patients with osteoporosis continues to increase in aging societies, including Japan. The first choice for managing osteoporotic vertebral compression fracture (OVF) is conservative treatment. Failure in conservative treatment for OVF may lead to non-union or vertebral collapse, resulting in neurological deficit and subsequently requiring surgical intervention. This multicenter nationwide study in Japan was conducted to comprehensively understand the outcomes of surgical treatments for OVF non-union. Methods: This multicenter, retrospective study included 403 patients (89 males, 314 females, mean age 73.8 ± 7.8 years, mean follow-up 3.9 ± 1.7 years) with neurological deficit due to vertebral collapse or non-union after OVF at T10-L5 who underwent fusion surgery with a minimum 1-year follow-up. Radiological and clinical outcomes at baseline and at the final follow-up (FU) were evaluated. Results: OVF was present at a thoracolumbar junction such as T12 (124 patients) and L1 (117 patients). A majority of OVF occurred after a minor trauma, such as falling down (55.3%) or lifting objects (8.4%). Short segment fusion, including affected vertebra, was conducted (mean 4.0 ± 2.0 vertebrae) with 256.8 minutes of surgery and 676.1 g of blood loss. A posterior approach was employed in 86.6% of the patients, followed by a combined anterior and posterior (8.7%), and an anterior (4.7%) approach. Perioperative complications and implant failures were observed in 18.1% and 41.2%, respectively. VAS scores of low back pain (74.7 to 30.8 mm) and leg pain (56.8 to 20.7 mm) improved significantly at FU. Preoperatively, 52.6% of the patients were unable to walk and the rate of non-ambulatory patients decreased to 7.5% at FU. Conclusions: This study demonstrated that substantial improvement in activity of daily living (ADL) was achieved by fusion surgery. Although there was a considerable rate of complications, fusion surgery is beneficial for elderly OVF patients with non-union.2019年, Spine surgery and related research, 3(4) (4), 361 - 367, 英語, 国内誌[査読有り]研究論文（学術雑誌）
- On the basis of rapid population aging, in 2007, the Japanese Orthopaedic Association (JOA) proposed a new disease concept "locomotive syndrome" as a degenerative condition of reduced mobility due to the impairment of the musculoskeletal system. Worsened locomotive components, which consist of bones, joints, and intervertebral discs, and muscles and nerves, can lead to symptoms such as pain, limited range of motion, malalignment, impaired balance, and difficulty in walking, ultimately resulting in the requirement of nursing care. "Locomotive syndrome" has gained increased interest in Japan but still not worldwide. Hence, in this brief review, we summarize an updated definition, assessment, and management of "locomotive syndrome". The JOA recommends "locomotion training" exercise intervention to be effective in maintaining motor function that comprises two simple exercises-squatting and single-leg standing. However, the extent to which exercises affect "locomotive syndrome" is unknown. Here, we further report hypothesis-generating patient cases who presented the improved sagittal spinopelvic alignment in standing radiographs and postural stability in piezoelectric force-plate measurements through our 6-month "locomotion training" outpatient rehabilitation program. It is noteworthy that "locomotion training" facilitated these improvements despite the presence of specific disorders including thoracic kyphosis and symptomatic lumbar spinal canal stenosis. This raises the need for further investigations to clarify effects of "locomotion training" exercises on the spinal alignment, global balance, and quality of life in patients with "locomotive syndrome".2019年, Advances in orthopedics, 2019, 6496901 - 6496901, 英語, 国際誌[査読有り]
- (株)南江堂, 2018年11月, 整形外科, 69(12) (12), 1232 - 1232, 日本語整形トピックス 脊椎椎間板変性へのオートファジーの関与とその脊索由来細胞における恒常性維持機構の可能性[査読有り]
- (株)医学書院, 2018年11月, 臨床整形外科, 53(11) (11), 951 - 957, 日本語椎間板研究の最前線 椎間板変性と炎症[査読有り]
- (株)医学書院, 2018年11月, 臨床整形外科, 53(11) (11), 975 - 980, 日本語椎間板研究の最前線 椎間板変性治療 オートファジー[査読有り]
- (株)三輪書店, 2018年11月, 脊椎脊髄ジャーナル, 31(11) (11), 1007 - 1012, 日本語【ハイテク機器を利用した最新の脊椎脊髄手術】「PediGuard」の使用経験[査読有り]
- (一社)日本脊椎脊髄病学会, 2018年09月, Journal of Spine Research, 9(9) (9), 1388 - 1393, 日本語ATG5の抑制を介したオートファジーの阻害はストレス環境下でヒト椎間板細胞においてアポトーシスとセネッセンスを誘導し、生存率を低下させる[査読有り]研究論文（学術雑誌）
- (一社)神緑会, 2018年08月, 神緑会学術誌, 34, 44 - 46, 日本語脊椎椎間板組織の恒常性維持におけるオートファジーの関与と役割の解明[査読有り]
- (株)北隆館, 2018年05月, 別冊Bio Clinica: 慢性炎症と疾患, 7(2) (2), 20 - 23, 日本語【整形外科疾患と慢性炎症】オートファジーと椎間板変性[査読有り]
- (一社)中部日本整形外科災害外科学会, 2018年01月, 中部日本整形外科災害外科学会雑誌, 61(1) (1), 175 - 176, 日本語ロコモティブシンドロームに対するロコモ体操の脊椎骨盤矢状面アライメントへの影響[査読有り]
- 2017年12月, Osteoarthritis and cartilage, 25(12) (12), 2134 - 2146, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)中部日本整形外科災害外科学会, 2017年11月, 中部日本整形外科災害外科学会雑誌, 60(6) (6), 1079 - 1080, 日本語がん患者の脊椎転移に対する直視下手術と経皮的後方固定術の全身状態、ADL、QOL改善効果[査読有り]研究論文（学術雑誌）
- STUDY DESIGN: A prospective cohort study of performance status (PS) and activities of daily living (ADL) in patients with spinal metastasis. OBJECTIVE: To identify the effect of spinal surgery on PS and ADL in patients with spinal metastasis. SUMMARY OF BACKGROUND DATA: Spinal metastasis causes severe neurological deficits, resulting in drastic loss of patients' PS and ADL. However, the effect of spine surgery on PS and ADL is not well known. MATERIALS AND METHODS: Seventy patients with spinal metastasis were enrolled in this study. Forty-six patients desired and underwent spine surgery ("surgery" group) and 24 patients did not desire surgery ("nonsurgery" group). Both groups received optimal treatments, including radiation, chemotherapy, and palliative care services. Evaluation was performed at 1, 3, and 6 months after study enrollment using the Eastern Cooperative Oncology Group PS, the Barthel index (BI) for ADL, and Frankel classification for neurological status. RESULTS: There was no significant difference in baseline PS, the BI, or Frankel classification between the groups. The surgery group showed significant improvement in PS, maintaining grade 2 or less throughout the duration of the study, as well as in ADL, exceeding 70 points of the BI, compared with the nonsurgery group (P<0.05). Significantly improved neurological condition was also observed in the surgery group over the following 6 months. More than 95% of patients who underwent surgery improved their PS, the BI, and neurological status. Furthermore, >80% of these patients maintained improvement in PS, the BI, and neurological status for at least 6 months. In contrast, PS, the BI, and neurological status of patients in the "nonsurgery" group deteriorated throughout the study period. CONCLUSIONS: Spine surgery improves PS, ADL, and neurological status in patients with spinal metastasis for a minimum 6 months. This indicates that these patients can acquire an independent daily life.2017年10月, Clinical spine surgery, 30(8) (8), E1026-E1032, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (株)全日本病院出版会, 2017年09月, 整形外科最小侵襲手術ジャーナル, (84) (84), 79 - 83, 日本語【転移性脊椎腫瘍に対する最小侵襲脊椎安定術(MISt)】転移性脊椎腫瘍に対する出張型骨転移Cancer Boardの取り組み[査読有り]
- 2017年08月, The spine journal : official journal of the North American Spine Society, 17(8) (8), 1163 - 1170, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- Mice expressing reduced levels of ERCC1-XPF (Ercc1-/Δ mice) demonstrate premature onset of age-related changes due to decreased repair of DNA damage. Muscle-derived stem/progenitor cells (MDSPCs) isolated from Ercc1-/Δ mice have an impaired capacity for cell differentiation. The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth in response to nutrient, hormone, and oxygen levels. Inhibition of the mTOR pathway extends the lifespan of several species. Here, we examined the role of mTOR in regulating the MDSPC dysfunction that occurs with accelerated aging. We show that mTOR signaling pathways are activated in Ercc1-/Δ MDSPCs compared with wild-type (WT) MDSPCs. Additionally, inhibiting mTOR with rapamycin promoted autophagy and improved the myogenic differentiation capacity of the Ercc1-/Δ MDSPCs. The percent of apoptotic and senescent cells in Ercc1-/Δ MDSPC cultures was decreased upon mTOR inhibition. These results establish that mTOR signaling contributes to stem cell dysfunction and cell fate decisions in response to endogenous DNA damage. Therefore, mTOR represents a potential therapeutic target for improving defective, aged stem cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1375-1382, 2017.2017年07月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 35(7) (7), 1375 - 1382, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 2017年06月, Journal of orthopaedic surgery (Hong Kong), 25(2) (2), 2309499017713917 - 2309499017713917, 英語[査読有り]研究論文（学術雑誌）
- 2017年06月, International orthopaedics, 41(6) (6), 1265 - 1271, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)中部日本整形外科災害外科学会, 2017年05月, 中部日本整形外科災害外科学会雑誌, 60(3) (3), 547 - 548, 日本語脊椎椎間板髄核におけるオートファジーの重要性とその誘導による椎間板変性予防の可能性[査読有り]研究論文（学術雑誌）
- 2017年04月, Spine, 42(8) (8), 556 - 564, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 金原出版(株), 2017年03月, 整形・災害外科, 60(3) (3), 279 - 285, 日本語【椎間板変性の病態と治療】椎間板の微小環境 細胞代謝、オートファジーの観点から[査読有り]
- (一社)中部日本整形外科災害外科学会, 2017年03月, 中部日本整形外科災害外科学会雑誌, 60(2) (2), 383 - 384, 日本語硬膜内髄外腫瘍に起因する水頭症により意識障害を呈した2例[査読有り]
- (一社)日本脊椎脊髄病学会, 2017年02月, Journal of Spine Research, 8(2) (2), 106 - 111, 日本語椎間板では他の筋骨格系組織よりもオートファジーの関与が大きく、その活性は変性とともに減少する[査読有り]研究論文（学術雑誌）
- (一社)日本脊椎脊髄病学会, 2017年02月, Journal of Spine Research, 8(2) (2), 139 - 146, 日本語脊椎転移に対する集学的治療の予後改善効果[査読有り]研究論文（学術雑誌）
- The authors present a case of 45-year-old man with neurofibromatosis type 1 (NF-1) and thoracic scoliosis, previously undergoing fusion surgery, who developed myelopathy. This patient further complained of lightning pain when he extended and horizontally abducted the convex-side shoulder. Radiological examination revealed the progression of dystrophic scoliosis with opened spinal canals and the presence of a neurofibroma behind the spinal cord at the apical levels. Delayed development of spinal instability can occur due to dystrophy even postoperatively in patients with NF-1. After tumor resection, he had rapid recovery from myelopathy and no recurrence of radiating pain despite shoulder movement. These findings provide a speculation that high, intense amplitude movement of the shoulder toward the spinal canal causes the impingement on the neurofibroma, resulting in indirect compression of the exposed spinal cord. This is the first report describing thoracic compression myelopathy associated with paraspinal displacement of the scapula.2017年01月, Journal of orthopaedic surgery (Hong Kong), 25(1) (1), 2309499016684726 - 2309499016684726, 英語, 国際誌[査読有り]
- Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model.BACKGROUND: Adipose tissue is a large endocrine organ known to secret adiponectin, which has anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Adiponectin is widely involved in systemic disease, diabetes mellitus, and cardiac infraction. This study aimed to investigate the involvement of adiponectin in intervertebral disc (IVD) degeneration. METHODS: Adipose and IVD tissues were obtained from human patients undergoing surgery (n = 4) and from skeletally mature Sprague-Dawley rats (n = 21). Tissues were stained immunohistochemically for adiponectin and adiponectin receptors AdipoR1 and AdipoR2. Changes in adiponectin receptor expression with IVD degeneration severity were then investigated using a rat tail temporary compression model. Rat IVD tissues were stained immunohistochemically with AdipoR1 or AdipoR2, and immunopositive cell percentages were calculated. Rat nucleus pulposus (NP) and annulus fibrosus (AF) tissues were isolated separately and treated with recombinant adiponectin (Ad 0.1 or 1.0 μg/ml) and/or interleukin-1 beta (IL-1β) (0.2 μg/ml) for 24 h. The four groups were as follows: control group (no treatment), IL-1β group (IL-1β-only treatment), IL-1β+Ad (0.1) group (IL-1β and adiponectin [0.1 μg/ml] treatment), and IL-1β+Ad (1.0) group (IL-1β and adiponectin [1.0 μg/ml]). Real-time reverse transcription-polymerase chain reaction was performed to evaluate messenger-RNA (mRNA) expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). RESULTS: Adiponectin was widely expressed in human subcutaneous and epidural adipose tissue. In rat IVD tissue, adiponectin was not observed in NP and AF. However, both AdipoR1 and AdipoR2 were widely expressed in both human and rat IVD tissues, with no significant differences in expression levels between receptors. Furthermore, expression levels of AdipoR1 and AdipoR2 were gradually decreased with increased IVD degeneration severity. Interestingly, mRNA expression levels of TNF-α and IL-6 were significantly upregulated by IL-1β stimulation. TNF-α expression in the IL-1β+Ad 1.0 group was significantly lower than that in the IL-1β group in both NP and AF cells (P < 0.05). Finally, IL-6 expression was not affected by adiponectin treatment in IVD cells. CONCLUSIONS: This study investigated for the first time the expression of adiponectin receptors in human and rat IVD cells. The findings indicate that adiponectin produced by the systemic or epidural adipose tissue may be involved in the pathomechanism of IVD degeneration.2016年11月, Journal of orthopaedic surgery and research, 11(1) (1), 147 - 147, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- 2016年08月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 34(8) (8), 1466 - 74, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (株)医学書院, 2016年07月, 臨床整形外科, 51(7) (7), 601 - 605, 日本語脊椎腫瘍 最近の話題 転移性脊椎腫瘍の診断と治療戦略 骨転移Cancer Boardの活用[査読有り]
- PURPOSE: Post-operative surgical site infection (SSI) is one of the most significant complications after instrumented spinal surgery. However, implant retention feasibility for early-onset multidrug-resistant SSI is still controversial. We aimed to verify our therapeutic strategy, surgical debridement with implant retention and long-term antimicrobial therapy for post-operative early-onset multidrug-resistant SSI. METHODS: We retrospectively analyzed the clinical course of 11 cases [eight men and three women, with a mean age of 70.4 (54-82) years] with early-onset multidrug-resistant SSI out of 409 consecutive cases of spinal instrumentation surgery performed between 2007 and 2013 at our institution. RESULTS: The median duration of follow-up was 868 (178-1,922) days. All SSIs were controlled, without recurrence during follow-up. The microbial pathogens were methicillin-resistant Staphylococcus aureus (seven cases), multidrug-resistant Corynebacterium (two cases), methicillin-resistant Staphylococcus epidermidis (one case), and methicillin-resistant coagulase-negative Staphylococcus aureus (one case). The mean duration from SSI diagnosis to surgery was 2.9 (1-6) days. Ten patients underwent surgical debridement with implant retention. No patients required multiple operations. All patients were given antimicrobial treatments. Mean duration of intravenous antimicrobials (vancomycin, vancomycin+ piperacillin/tazobactam, or gentamicin) was 66.5 (12-352) days and 336 (89-1,673) days for oral antimicrobials (rifampicin + sulfamethoxazole/trimethoprim, sulfamethoxazole/trimethoprim, or minomycin). The mean duration of clinical signs and symptom recovery was 31.0 (7-73) days, and the mean time for normalization of C-reactive protein was 54.5 (7-105) days. CONCLUSIONS: Early-onset multidrug-resistant SSI was successfully treated by surgical debridement with implant retention and long-term antimicrobial therapy.2016年06月, International orthopaedics, 40(6) (6), 1171 - 7, 英語, 国際誌[査読有り]
- (一社)中部日本整形外科災害外科学会, 2016年01月, 中部日本整形外科災害外科学会雑誌, 59(1) (1), 201 - 202, 日本語重度症候性側彎症例への椎弓根スクリュー刺入における電磁波センサー付きプローブの有用性[査読有り]
- (一社)日本脊椎脊髄病学会, 2016年01月, Journal of Spine Research, 7(1) (1), 25 - 30, 日本語70歳以上脊椎転移に対する手術成績[査読有り]研究論文（学術雑誌）
- (一社)日本脊椎脊髄病学会, 2015年10月, Journal of Spine Research, 6(10) (10), 1535 - 1538, 日本語重症骨粗鬆症に伴う多発脊椎椎体骨折に対する手術的治療の問題点と対策[査読有り]
- INTRODUCTION: Nutrient deprivation is a likely contributor to intervertebral disc (IVD) degeneration. Silent mating type information regulator 2 homolog 1 (SIRT1) protects cells against limited nutrition by modulation of apoptosis and autophagy. However, little evidence exists regarding the extent to which SIRT1 affects IVD cells. Therefore, we conducted an in vitro study using human IVD nucleus pulposus (NP) cells. METHODS: Thirty-two IVD specimens were obtained from patients who underwent surgical intervention and were categorized based on Pfirrmann IVD degeneration grades. Cells were isolated from the NP and cultured in the presence of recombinant human SIRT1 (rhSIRT1) under different serum conditions, including 10 % (v/v) fetal bovine serum (FBS) as normal nutrition (N) and 1 % (v/v) FBS as low nutrition (LN). 3-Methyladenine (3-MA) was used to inhibit autophagy. Autophagic activity was assessed by measuring the absorbance of monodansylcadaverine and immunostaining and Western blotting for light chain 3 and p62/SQSTM1. Apoptosis and pathway analyses were performed by flow cytometry and Western blotting. RESULTS: Cells cultured under LN conditions decreased in number and exhibited enhanced autophagy compared with the N condition. Medium supplementation with rhSIRT1 inhibited this decrease in cell number and induced an additional increase in autophagic activity (P < 0.05), whereas the combined use of rhSIRT1 and 3-MA resulted in drastic decreases in cell number and autophagy (P < 0.05). The incidence of apoptotic cell death increased under the LN condition, which was decreased by rhSIRT1 (P < 0.05) but increased further by a combination of rhSIRT1 and 3-MA (P < 0.05). Under LN conditions, NP cells showed a decrease in antiapoptotic Bcl-2 and an increase in proapoptotic Bax, cleaved caspase 3, and cleaved caspase 9, indicating apoptosis induction via the mitochondrial pathway. These changes were suppressed by rhSIRT1 but elevated further by rhSIRT1 with 3-MA, suggesting an effect of rhSIRT1-induced autophagy on apoptosis inhibition. Furthermore, the observed autophagy and apoptosis were more remarkable in cells from IVDs of Pfirrmann grade IV than in those from IVDs of Pfirrmann grade II. CONCLUSIONS: SIRT1 protects against nutrient deprivation-induced mitochondrial apoptosis through autophagy induction in human IVD NP cells, suggesting that rhSIRT1 may be a potent treatment agent for human degenerative IVD disease.2015年09月, Arthritis research & therapy, 17, 253 - 253, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (公社)日本整形外科学会, 2015年09月, 日本整形外科学会雑誌, 89(9) (9), 579 - 584, 日本語椎間板変性と臨床 未来への展望 椎間板変性の発生機序と臨床との関連について[査読有り]
- Mechanical loading is a salient factor in the progression of spinal disorders that contribute to back pain. Biological responses to loading modes like flexion/extension (F/E) in relevant spinal tissues remain unstudied. A novel, multi-axial experimental system was developed to subject viable functional spinal units (FSUs) to complex, in-situ loading. The objective was to determine biological effects of F/E in multiple spinal tissues-annulus fibrosus, nucleus pulposus, facet cartilage, and ligamentum flavum. Rabbit lumbar FSUs were mounted in a bioreactor within a robotic testing system. FSUs underwent small (0.17/0.05 Nm) and large (0.5/0.15 Nm) range-of-motion F/E for 1 or 2 h of cycling. Outcomes in each tissue, compared to unloaded FSUs, included (i) relative mRNA expression of catabolic (MMP-1, 3 and ADAMTS-5), pro-inflammatory (COX-2), and anabolic (ACAN) genes and (ii) immunoblotting of aggrecan degradation. Total energy applied to FSUs increased in groups subject to large range-of-motion and 2-h cycling, and moment relaxation was higher with large range-of-motion. F/E significantly modulated MMP1,-3 and COX-2 in facet cartilage and MMP-3 and ACAN in annulus fibrosus. Large range-of-motion loading increased MMP-mediated aggrecan fragmentation in annulus fibrosus. Biological responses to complex loading ex vivo showed variation among spinal tissues that reflect tissue structure and mechanical loading in F/E.2015年08月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 33(8) (8), 1255 - 64, 英語, 国際誌[査読有り]
- (株)メジカルビュー社, 2015年04月, 関節外科, 34(4月増刊) (4月増刊), 27 - 39, 日本語【整形外科基礎の最前線2015】椎間板変性の機序と再生の可能性 基礎研究から臨床研究まで[査読有り]
- 2015年04月, Coluna/ Columna, 14(2) (2), 77 - 81[査読有り]研究論文（学術雑誌）
- 2015年03月, Cochrane Database of Systematic Reviews, 2015(3) (3)[査読有り]研究論文（学術雑誌）
- BACKGROUND CONTEXT: Intervertebral disc (IVD) degeneration, a major cause of low back pain, is considered to be induced by daily mechanical loading. Mechanical stress is widely known to affect cell survival and extracellular matrix metabolism in many cell types. Although the involvement of integrin α5β1 transmembrane mechanoreceptor in IVD degeneration has been reported, the precise function of integrin α5β1 remains obscure. PURPOSE: To reflect IVD tissue response to mechanical stress using a dynamic loading organ culture system and elucidate the functional impact of integrin α5β1 on the pathomechanism of IVD degeneration. STUDY DESIGN: An ex vivo study using a dynamic loading organ culture system. METHODS: Ninety-six rat IVD explants were examined. Intervertebral discs were subjected to 1.3 MPa, 1.0 Hz dynamic compressive load in the presence or absence of an Arg-Gly-Asp (RGD) peptide with affinity to the fibronectin binding-site of integrin α5β1. Cell viability and histomorphology were assessed. The localization of integrin α5β1 in the IVD was assessed by immunohistochemistry. Gene expression levels of IVD cells were evaluated using real-time reverse transcription-polymerase chain reaction. RESULTS: In the nucleus pulposus (NP), cell density and viability were reduced by dynamic compressive load. Histologic degenerative alterations, mainly seen in the NP, were the morphologic changes of NP cells. In both NP and annulus fibrosus (AF), immunohistochemistry revealed localization of integrin α5β1 and that the messenger-RNA expression of integrin α5β1 was increased by dynamic load. Dynamic load induced a catabolic effect, the stimulation of matrix metalloproteinase-3 and -13 gene expressions by NP and AF cells. The RGD peptide partially blocked the histologic alterations and the catabolic effect. CONCLUSIONS: The dynamic loading organ culture system simulated cellular responses to mechanical loading of the IVD. Our results suggest that IVD cells recognize the mechanical stress through RGD integrins, particularly the α5β1 subtype that is highly expressed in NP and AF cells. Further experiments using this system will provide information about pathomechanisms of IVD degeneration through the mechanotransduction pathways.2015年03月, Spine J, 15(3) (3), 417 - 26, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- (一社)日本脊椎脊髄病学会, 2015年02月, Journal of Spine Research, 6(2) (2), 170 - 175, 日本語10年間におけるRA頸椎不安定性の進行 外来通院患者の前向き多施設共同研究[査読有り]
- DNA damage is a cause of age related pathologies, including osteoarthritis (OA). Excision repair cross complementation group 1 (ERCC1) is an endonuclease required for DNA damage repair. In this study we investigated the function of ERCC1 in chondrocytes and its association with the pathophysiology of OA. ERCC1 expression in normal and osteoarthritic cartilage was assessed, as were changes in ERCC1 expression in chondrocytes under catabolic stress. Inhibiting ERCC1 in chondrocytes under interleukin-1β stimulation using small interfering RNA (siRNA) was also evaluated. Finally, cellular senescence and apoptosis were examined in relation to ERCC1 function. ERCC1 expression was decreased in OA cartilage and increased within 4 h of exposure to interleukin (IL)-1β, but decreased after 12 h. The inhibition of ERCC1 by siRNA increased the expression of matrix metallopeptidase 13 and decreased collagen type II. ERCC1 inhibition also increased the number of apoptotic and senescent cells. The inhibition of ERCC1 in chondrocytes increased their expression of OA related proteins, apoptosis, cellular senescence, and hypertrophic-like changes which suggest that ERCC1 is critical for protecting human chondrocytes (HCs) from catabolic stresses and provides insights into the pathophysiology of OA and a potential target for its treatment. (191)2014年10月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 32(10) (10), 1326 - 32, 英語, 国際誌[査読有り]
- (株)三輪書店, 2014年09月, 脊椎脊髄ジャーナル, 27(9) (9), 816 - 822, 日本語【脊椎疾患の自然経過と治療選択】リウマチ性頸椎不安定性の自然経過[査読有り]
- (公社)日本整形外科学会, 2014年05月, 日本整形外科学会雑誌, 88(5) (5), 368 - 375, 日本語脊椎疾患の自然経過解明への挑戦 リウマチ環軸関節亜脱臼の自然経過[査読有り]
- The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and non-notochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2α-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration.2014年03月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 32(3) (3), 455 - 63, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- OBJECTIVE: To test whether the interaction between annulus fibrosus cells (AFCs) and endothelial cells (ECs) disrupts matrix homeostasis and stimulates production of innervation mediators. METHODS: Human microvascular ECs were cultured in the conditioned media of AF cell culture derived from degenerated human surgical specimen. Matrix-metalloproteinases (MMPs) and platelet-derived growth factor (PDGF) of ECs of this culture were analyzed by qRT-PCR, Western, and immunofluorescence. Vascular endothelial growth factor (VEGF), Interleukin-8 (IL-8), and nerve growth factor (NGF) in the media of this cell culture were assayed by ELISA. To determine the effects of ECs on AFCs, qRT-PCR was performed to determine mRNA levels of collagen I, II and aggrecan in AFCs cultured in EC conditioned media. RESULTS: Compared to ECs cultured in naïve media, ECs exposed to AFC conditioned media expressed higher mRNA and protein levels of key biomarkers of invasive EC phenotype, MMP-2 (2×), MMP-13 (4×), and PDGF-B (1.5-2×), and NGF (24.9 ± 15.2 pg/mL vs 0 in naïve media). Treatment of AF cells with EC culture conditioned media decreased collagen type II expression two fold. Considerable quantities of pro-angiogenic factors IL-8 (396.7 ± 302.0 pg/mL) and VEGF (756.2 ± 375.9 pg/mL) were also detected in the conditioned media of untreated AF cell culture. DISCUSSION: AFCs from degenerated discs secreted factors which stimulated EC production of factors known to induce matrix degradation, angiogenesis, and innervation. IL-8 and VEGF maybe the secreted factors from AFCs which mediate a pro-angiogenic stimulus often implicated in the development of disc degeneration.2014年02月, Osteoarthritis and cartilage, 22(2) (2), 344 - 54, 英語, 国際誌[査読有り]
- INTRODUCTION: The intervertebral disc has a complex structure originating developmentally from both the mesenchyme and notochord. Notochordal cells disappear during adolescence, which is also when human discs begin to show degenerative signs. During degeneration later in life, disc cells decline because of apoptosis. Although many animal models have been developed to simulate human disc degeneration, few studies have explored the long-term changes in cell population and phenotype. Our objective was to elucidate the time-dependent notochordal cell disappearance and apoptotic cell death in a rat tail static compression-induced disc degeneration model. METHODS: Twenty-four 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device and loaded statically at 1.3 MPa for up to 56 days. Loaded and distal-unloaded discs were harvested. Changes in cell number and phenotype were assessed with histomorphology and immunofluorescence. Apoptosis involvement was determined with terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining and immunohistochemistry. RESULTS: The number of disc nucleus pulposus and annulus fibrosus cells decreased with the loading period; particularly, the decrease was notable at day 7 in larger, vacuolated, cytokeratin-8- and galectin-3-co-positive cells, indicating notochordal origin. Subsequently, the proportion of cells positive for TUNEL and cleaved caspase-3, markers of apoptosis induction, increased from day 7 through day 56. Although the percentage of cells immunopositive for cleaved caspase-8, a marker of apoptosis initiation through the death-receptor pathway, increased only at day 7, the percentage of cells immunopositive for cleaved caspase-9 and p53-regulated apoptosis-inducing protein 1 (p53AIP1), markers of apoptosis initiation through the p53-mediated mitochondrial pathway, increased from day 7 through day 56. The percentage of cells immunopositive for B-cell lymphoma 2 (Bcl-2) and silent mating type information regulation 2 homolog 1 (SIRT1), antiapoptotic proteins, decreased consistently with compression. CONCLUSIONS: This rat tail model mimics notochordal cell disappearance and apoptotic cell death in human disc aging and degeneration. Sustained static compression induces transient activation of apoptosis through the death-receptor pathway and persistent activation of apoptosis through the p53-mediated mitochondrial pathway in disc cells. The increased proapoptotic and decreased antiapoptotic proteins observed at all time points signify static compression-induced disc cell death and degeneration.2014年01月, Arthritis research & therapy, 16(1) (1), R31, 英語, 国際誌[査読有り]
- OBJECTIVE: To clarify the incidence and predictive risk factors of cervical spine instabilities which may induce compression myelopathy in patients with rheumatoid arthritis (RA). METHODS: Three types of cervical spine instability were radiographically categorized into "moderate" and "severe" based on atlantoaxial subluxation (AAS: atlantodental interval >3 mm versus ≥10 mm), vertical subluxation (VS: Ranawat value <13 mm versus ≤10 mm), and subaxial subluxation (SAS: irreducible translation ≥2 mm versus ≥4 mm or at multiple). 228 "definite" or "classical" RA patients (140 without instability and 88 with "moderate" instability) were prospectively followed for >5 years. The endpoint incidence of "severe" instabilities and predictors for "severe" instability were determined. RESULTS: Patients with baseline "moderate" instability, including all sub-groups (AAS(+) [VS(-) SAS(-)], VS(+) [SAS(-) AAS(±)], and SAS(+) [AAS(±) VS(±)]), developed "severe" instabilities more frequently (33.3% with AAS(+), 75.0% with VS(+), and 42.9% with SAS(+)) than those initially without instability (12.9%; p<0.003, p<0.003, and p = 0.061, respectively). The incidence of cervical canal stenosis and/or basilar invagination was also higher in patients with initial instability (17.5% with AAS(+), 37.5% with VS(+), and 14.3% with SAS(+)) than in those without instability (7.1%; p = 0.028, p<0.003, and p = 0.427, respectively). Multivariable logistic regression analysis identified corticosteroid administration, Steinbrocker stage III or IV at baseline, mutilating changes at baseline, and the development of mutilans during the follow-up period correlated with the progression to "severe" instability (p<0.05). CONCLUSIONS: This prospective cohort study demonstrates accelerated development of cervical spine involvement in RA patients with pre-existing instability--especially VS. Advanced peripheral erosiveness and concomitant corticosteroid treatment are indicators for poor prognosis of the cervical spine in RA.2014年, PloS one, 9(2) (2), e88970, 英語, 国際誌[査読有り]
- STUDY DESIGN: A laboratory investigation using porcine model. OBJECTIVE: To clarify the effectiveness of the soft coagulation system for stopping bleeding from the epidural vein using different outputs and the safety in terms of tissue damage including spinal cord injury. SUMMARY OF BACKGROUND DATA: Problems associated with coagulation using an electrosurgical device, such as carbonization of tissue or adhesion to the electrode, have been highlighted. So called "soft coagulation" has been developed to solve these problems. Its' utility as well as the safety of the neural structure in spine surgery has never been reported. METHODS: A total of 3 animals and 45 spinal segments were used. Total laminectomy was performed to expose the dural tube and epidural venous plexus. Stable bleeding was induced by a 22 G needle puncture. Soft coagulation monopolar output (SCM), soft coagulation bipolar output (SCB), and conventional bipolar output (CB) were used as the coagulators. Valid hemostasis was defined as macroscopically complete bleeding stoppage by coagulation within 3 minutes. The neurological assessment was evaluated by somatosensory evoked potential. Histologic analysis was performed to determine the area of thermal damage. RESULTS: Valid hemostasis ratio was 75.0% of SCM group, 68.8% of SCB group, and 30.8% of CB group. Somatosensory evoked potential monitoring revealed that spinal cord injury was observed in 4 lesions (25%) of the SCM group. Neither bipolar groups (SCB and CB) showed any changes in waveform pattern. Histologic analysis revealed that severe thermal damages were observed in the epidural space of the SCM group. CONCLUSIONS: The usefulness of soft coagulation is revealed in terms of bleeding stoppage from epidural vessels and reduced soft-tissue damage compared with the conventional electric device. However, assessing the potential risk of severe neural tissue damage including spinal cord injury, a bipolar soft coagulation is strongly recommended for use in spine surgery.2013年10月, Journal of spinal disorders & techniques, 26(7) (7), E281-5 - 5, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: A retro-odontoid pseudotumor is usually a reactive fibrocartilaginous mass associated with atlantoaxial subluxation (AAS). However, a retro-odontoid pseudotumor not associated with AAS, which undergoes spontaneous regression following C1 laminoplasty, has been reported. The purpose of this study was to report surgical outcomes of C1 laminectomy for retro-odontoid pseudotumor without AAS. MATERIALS AND METHODS: The cases of seven patients (mean age 75.6 ± 7.6 years-old) with retro-odontoid pseudotumor without AAS were reviewed. The mean follow up time was 52.3 ± 25.5 months. Each patient underwent a C1 laminectomy with an additional C3-6 expansion laminoplasty in three patients. The Japanese Orthopaedic Association score (JOA score) was used for neurological assessment. Pseudotumor size and additional AAS were analyzed using MRI and radiography. RESULTS: All patients exhibited neurological improvement following surgery, the JOA score improved from 7.2 ± 3.2 to 14.1 ± 2.6. The mean O-C2 and C2-7 angle decreased from -3.2 ± 2.1° to -3.9 ± 1.7°, showing a slight kyphotic change. Postoperative AAS was not observed. All pseudotumors spontaneously resolved, and recurrence and regrowth were not observed. Five patients had MRIs after gadolinium administration; four patients who showed enhancement of the pseudotumor had almost complete reduction within 1 year following surgery. DISCUSSION: Our study, assessing the outcome of C1 laminectomy for retro-odontoid pseudotumor, found neurological improvement in all cases. Since all pseudotumors were reduced and additional AAS was not observed, C1 laminectomy for retro-odontoid pseudotumor, in the absence of AAS, is recommended as a therapeutic strategy.2013年05月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 22(5) (5), 1119 - 26, 英語, 国際誌[査読有り]
- It is suggested that pro-inflammatory cytokines, which are produced by interaction of the intervertebral nucleus pulposus cells and macrophages, may be linked to the cause of pain of the intervertebral disc herniation. This study carries out the in vitro experiments to examine the mechanism, with the use of the co-culture of an immortalized cell line of nucleus pulposus of the human intervertebral disc and the macrophage cell line. As a result, it is found that the production of pro-inflammatory cytokines is significantly larger at the co-culture group than at the independent culture group. Also, at the co-culture group of macrophages and intervertebral nucleus pulposus cells with over-expression of fas ligand (FasL), the production of pro-inflammatory cytokines is found to be far larger. Furthermore, it is found that these pro-inflammatory cytokines are produced mainly by the intervertebral nucleus pulposus cells with over-expression of FasL, and that the expression of a disintegrin and metalloproteinase (ADAM) 10, which controls the expression of FasL and activates reverse signaling inside cells, also increases. From these findings, it is suggested that FasL and ADAM10 play an important role in the production of pro-inflammatory cytokines coming from interaction of the intervertebral nucleus pulposus cells and macrophages.2013年04月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 31(4) (4), 608 - 15, 英語, 国際誌[査読有り]
- (株)南江堂, 2013年04月, 別冊整形外科, (63) (63), 100 - 102, 日本語【腰椎疾患up-to-date】腰椎疾患に対する保存的治療 神経症状に対する薬物治療 腰部脊柱管狭窄症に伴う根性痛に対するプレガバリンの効果と投与上の留意点[査読有り]研究論文（学術雑誌）
- BACKGROUND CONTEXT: Destruction of extracellular matrix (ECM) leads to intervertebral disc degeneration (IDD), which underlies many spine-related disorders. Matrix metalloproteinases (MMPs), and disintegrins and metalloproteinases with thrombospondin motifs (ADAMTSs) are believed to be the major proteolytic enzymes responsible for ECM degradation in the intervertebral disc (IVD). PURPOSE: To summarize the current literature on gene expression and regulation of MMPs, ADAMTSs, and tissue inhibitors of metalloproteinases (TIMPs) in IVD aging and IDD. METHODS: A comprehensive literature review of gene expression of MMP, ADAMTS, and TIMP in human IDD and reported studies on regulatory factors controlling their expressions and activities in both human and animal model systems. RESULTS: Upregulation of specific MMPs (MMP-1, -2, -3, -7, -8, -10, and -13) and ADAMTS (ADAMTS-1, -4, and -15) were reported in human degenerated IVDs. However, it is still unclear from conflicting published studies whether the expression of ADAMTS-5, the predominant aggrecanase, is increased with IDD. Tissue inhibitors of metalloproteinase-3 is downregulated, whereas TIMP-1 is upregulated in human degenerated IVDs relative to nondegenerated IVDs. Numerous studies indicate that the expression levels of MMP and ADAMTS are modulated by a combination of many factors, including mechanical, inflammatory, and oxidative stress, some of which are mediated in part through the p38 mitogen-activated protein kinase pathway. Genetic predisposition also plays an important role in determining gene expression of MMP-1, -2, -3, and -9. CONCLUSIONS: Upregulation of MMP and ADAMTS expression and enzymatic activity is implicated in disc ECM destruction, leading to the development of IDD. Future IDD therapeutics depends on identifying specific MMPs and ADAMTSs whose dysregulation result in pathological proteolysis of disc ECM.2013年03月, The spine journal : official journal of the North American Spine Society, 13(3) (3), 331 - 41, 英語, 国際誌[査読有り]
- STUDY DESIGN: A prospective minimum 5-year follow-up study of the cervical spine in patients with rheumatoid arthritis (RA) initially without cervical involvement. OBJECTIVE: To clarify the incidence and aggravation of cervical spine instabilities and their predictive risk factors in patients with RA. SUMMARY OF BACKGROUND DATA: Many reports have shown the progression of cervical spine involvement in RA. However, few articles have described comprehensive evaluation of its prognostic factors. METHODS: A total of 140 patients with "definite" or "classical" RA initially without cervical involvement were prospectively followed for more than 5 years. Radiographical cervical findings were classified into 3 instabilities: atlantoaxial subluxation (AAS: atlantodental interval >3 mm), vertical subluxation (VS: Ranawat value <13 mm), and subaxial subluxation (SAS: irreducible translation ≥ 2 mm). "Severe" extents were defined as AAS with atlantodental interval 10 mm or more, VS with Ranawat value 10 mm or less, and SAS with translation 4 mm or more or at multiple levels. Incidence of these developments and predictors for "severe" instabilities were investigated. RESULTS: During 6.0 ± 0.5 years, 43.6% of 140 patients developed cervical instabilities: AAS in 32.1%, VS in 11.4%, and SAS in 16.4% with some combinations. "Severe" instabilities were exhibited in 12.9% of patients: AAS in 3.6%, VS in 6.4%, and SAS in 5.0%. Furthermore, 4.3% presented canal stenosis, with 13 mm or less space available for the spinal cord (SAC) due to "severe" AAS or "severe" VS in 2.9% and 12 mm or less SAC due to "severe" SAS in 2.1%. Multivariable logistic regression analysis identified corticosteroid administration, mutilating changes at baseline, and the development of nonmutilating into mutilating changes during the follow-up period correlated with "severe" instabilities (P < 0.05). CONCLUSION: A minimum 5-year follow-up reveals the occurrence of cervical instabilities in 43.6%, "severe" aggravation in 12.9%, and decreased SAC in 4.3% of patients with RA. Characteristics of severe disease activity-established mutilating changes, progressive development into mutilating changes, and potentially concomitant corticosteroid treatment-are indicators for poor prognosis of the cervical spine in RA.2012年12月, Spine, 37(26) (26), 2136 - 44, 英語, 国際誌[査読有り]
- INTRODUCTION: Little is known about when and how progressive spondylolisthesis occurs. In this report segmental motion related to age and disc degeneration at L4/5 disc was investigated. MATERIALS AND METHODS: 637 patients with low back and/or leg pain underwent radiologic and MRI examinations simultaneously. Because 190 patients with conditions which might impede accurate measurement were excluded, 447 patients, comprising 268 men and 179 women, were included; age range, was 10-86 (mean: 53) years. Three radiologic parameters slip in neutral position (mm), sagittal translation (mm), and segmental angulation (degrees) were examined at the L4/5 segment. On T2-weighted MRI, severity of disc degeneration at L4/5 was classified by Pfirrmann's criteria, grade 1-5. RESULTS: Results showed stage of disc degeneration that progressed according to aging with significant differences except for between grades 4 and 5. Amount of anterior slip was small among grades 1 to 3; however, it greatly increased between grades 3 and 4 and between grades 4 and 5, suggesting that grade 3 disc degeneration has a potential risk of future progression of anterior slip. This finding may also suggest that once significant slip occurs, it will progress to the final grade. Furthermore, the grade 3 degeneration group exhibited large amounts of motion in both angulation and translation, suggesting it was the most unstable group. CONCLUSION: Our results with radiography and MRI indicate that grade 3 disc degeneration is a critical stage for the progression of lumbar spondylolisthesis at L4/5 segment.2012年11月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 21(11) (11), 2134 - 9, 英語, 国際誌[査読有り]
- OBJECTIVE: The expression of proinflammatory factors such as tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-8, and prostaglandin E(2) (PGE(2) ) is significantly correlated with the symptoms of herniated disc disease. Among the different types of immune cells, macrophages are frequently noted in the herniated disc tissue. We undertook this study to clarify the interaction of the intervertebral disc (IVD) and macrophages with regard to the production of TNFα, IL-6, IL-8, and PGE(2) . METHODS: We developed 2 animal models to assess the interactions of IVDs with macrophages in terms of TNFα, IL-6, IL-8, and PGE(2) production and pain-related behavior. We also cocultured IVDs and macrophages to assess the role of TNFα in IL-6, IL-8, and PGE(2) production. RESULTS: IVD autografts induced TNFα, IL-6, IL-8, and cyclooxygenase 2 (COX-2) messenger RNA (mRNA) up-regulation; macrophage infiltration was seen shortly after the autograft was implanted. A significant decrease was noted in the mechanical threshold of the ipsilateral paw following the up-regulation of TNFα, IL-6, IL-8, and COX-2 mRNA. Only IVD and macrophage cocultures resulted in IL-8 and PGE(2) up-regulation. TNFα up-regulation was maximized before that of IL-6 and IL-8. TNFα neutralization attenuated production of IL-6 and PGE(2) , but not that of IL-8. Neutralization of TNFα and IL-8 significantly increased the paw withdrawal mechanical threshold in the IVD autograft and spinal nerve ligation model. CONCLUSION: IVD-macrophage interaction plays a major role in sciatica and in the production of TNFα, IL-6, IL-8, and PGE(2) . TNFα is required for IL-6 and PGE(2) production, but not for IL-8 production, during IVD-macrophage interaction. Neutralization of TNFα and IL-8 can be a valuable therapy for herniated disc disease.2012年08月, Arthritis and rheumatism, 64(8) (8), 2601 - 10, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- PURPOSE: A procedure using an interspinous process spacer (IPS) was recently developed for the treatment of posture-dependent lumbar spinal-canal stenosis (LSS) patients. We developed a novel IPS which can be inserted with simpler procedures and removed percutaneously. The objectives of this study were: (1) to evaluate the feasibility and safety of this novel technique, and (2) to assess the effectiveness of this spacer in terms of preventing an increase of epidural pressure in lumbar extension using a porcine model. METHODS: Eight young pigs were used. Under general anesthesia and image guidance, the spacers were inserted. Three months after operation, MR images were taken and all spacers were removed. Blood samples were obtained before and 1, 3, 7 days after surgery. After killing the animals, the lumbar spines were observed macroscopically. Another six animals were used. Under general anesthesia and image guidance, a flexible pressure transducer was inserted into the epidural space and epidural pressure was measured in neutral and at maximum extension with and without spacer insertion. RESULTS: Percutaneous insertion and removal of the spacer was successful for all animals through small skin incisions. MR images showed minimal damage to the muscle. No significant up-regulation of Interleukin-6 (IL-6) and CRP was detected. Macroscopic observation of the lumbar spine 3 months after the operation revealed that the area of the interspinous process contacting with the inserted spacer showed some bone erosion/remodeling. Insertion of the spacer did not affect the epidural pressure in neutral but significantly prevented an increase of epidural pressure in lumber extension. CONCLUSIONS: This study demonstrated that the percutaneous insertion and removal of a novel IPS was feasible and safe using a simple technique. Furthermore, this procedure can be recognized as minimally invasive surgery from the viewpoint of skin incision, short insertion track, inflammatory mediators, and muscle damage. Improvements should be attempted in future studies using softer or more elastic materials for the spacer to lessen bone erosion/remodeling at contacting area of the inserted spacer.2012年06月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 21(6) (6), 1178 - 85, 英語, 国際誌[査読有り]
- (株)三輪書店, 2012年04月, 脊椎脊髄ジャーナル, 25(4) (4), 439 - 443, 日本語【腰痛のサイエンス】(第8章)腰痛関連因子 腰痛と遺伝子 椎間板再生と遺伝子[査読有り]
- INTRODUCTION: The longitudinal degradation mechanism of extracellular matrix (ECM) in the interbertebral disc remains unclear. Our objective was to elucidate catabolic and anabolic gene expression profiles and their balances in intervertebral disc degeneration using a static compression model. METHODS: Forty-eight 12-week-old male Sprague-Dawley rat tails were instrumented with an Ilizarov-type device with springs and loaded statically at 1.3 MPa for up to 56 days. Experimental loaded and distal-unloaded control discs were harvested and analyzed by real-time reverse transcription-polymerase chain reaction (PCR) messenger RNA quantification for catabolic genes [matrix metalloproteinase (MMP)-1a, MMP-2, MMP-3, MMP-7, MMP-9, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5], anti-catabolic genes [tissue inhibitor of metalloproteinases (TIMP)-1, TIMP-2, and TIMP-3], ECM genes [aggrecan-1, collagen type 1-α1, and collagen type 2-α1], and pro-inflammatory cytokine genes [tumor necrosis factor (TNF)-α, interleukin (IL)-1α, IL-1β, and IL-6]. Immunohistochemistry for MMP-3, ADAMTS-4, ADAMTS-5, TIMP-1, TIMP-2, and TIMP-3 was performed to assess their protein expression level and distribution. The presence of MMP- and aggrecanase-cleaved aggrecan neoepitopes was similarly investigated to evaluate aggrecanolytic activity. RESULTS: Quantitative PCR demonstrated up-regulation of all MMPs and ADAMTS-4 but not ADAMTS-5. TIMP-1 and TIMP-2 were almost unchanged while TIMP-3 was down-regulated. Down-regulation of aggrecan-1 and collagen type 2-α1 and up-regulation of collagen type 1-α1 were observed. Despite TNF-α elevation, ILs developed little to no up-regulation. Immunohistochemistry showed, in the nucleus pulposus, the percentage of immunopositive cells of MMP-cleaved aggrecan neoepitope increased from 7 through 56 days with increased MMP-3 and decreased TIMP-1 and TIMP-2 immunopositivity. The percentage of immunopositive cells of aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with decreased TIMP-3 immunopositivity. In the annulus fibrosus, MMP-cleaved aggrecan neoepitope presented much the same expression pattern. Aggrecanase-cleaved aggrecan neoepitope increased at 7 and 28 days only with increased ADAMTS-4 and ADAMTS-5 immunopositivity. CONCLUSIONS: This rat tail sustained static compression model mimics ECM metabolic imbalances of MMPs, aggrecanases, and TIMPs in human degenerative discs. A dominant imbalance of MMP-3/TIMP-1 and TIMP-2 relative to ADAMTS-4 and ADAMTS-5/TIMP-3 signifies an advanced stage of intervertebral disc degeneration.2012年03月, Arthritis research & therapy, 14(2) (2), R51, 英語, 国際誌[査読有り]
- (株)三輪書店, 2012年01月, 脊椎脊髄ジャーナル, 25(1) (1), 33 - 38, 日本語【関節リウマチ(RA)頸椎病変の治療戦略】関節リウマチ(RA)頸椎病変の手術適応と術式選択 病変進行の観点から[査読有り]
- (一社)日本脊椎脊髄病学会, 2011年09月, Journal of Spine Research, 2(9) (9), 1447 - 1453, 日本語リウマチ性頸椎不安定性の発生とその重症化 不安定性を認めない症例に対する前向き追跡調査[査読有り]
- House-keeping genes (HKGs) are generally used as endogenous controls for molecular normalization in quantitative PCR analysis. However, whether all the so-called HKGs are useful for intervertebral disc research is controversial. Our objective was, using a prevalidated rat tail static compression loading-induced disc degeneration model, to clarify the feasibility of common HKGs for gene-quantification in the nucleus pulposus cells. In real-time RT-PCR for five HKGs [β-actin, β-glucuronidase, β-2 microglobulin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and lactate dehydrogenase A (LDHA)], static compression at 1.3 MPa for up to 56 days demonstrated messenger RNA (mRNA) expression levels of consistent β-2 microglobulin and GAPDH, slightly up-regulated β-glucuronidase, and fairly down-regulated β-actin and LDHA. Especially, β-actin had a drastic suppression to 0.15-fold in the loaded relative to unloaded discs at 7 days. In immunofluorescence, β-actin showed a significant down-regulation to almost undetectable levels from 28 days, while GAPDH was constantly detected throughout. β-Actin mRNA and protein-distribution are thought to be affected by the loading treatment, however, GAPDH mRNA and protein-distribution can retain relatively stable expressions. Under prolonged static compression, β-actin and probably LDHA are inappropriate, and GAPDH is a feasible HKG as internal references in the disc cells.2011年08月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 29(8) (8), 1284 - 90, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- STUDY DESIGN: A 5-year prospective cohort study of cervical spine instabilities in rheumatoid arthritis (RA). OBJECTIVE.: To clarify the natural course of cervical instabilities in RA patients and to determine predictors for the prognosis of RA cervical spine. SUMMARY OF BACKGROUND DATA: Although several previous studies investigating the natural history of RA cervical spine have been reported, few of them have described radiological predictive factors for the aggravation of these instabilities. METHODS: Two hundred sixty-seven outpatients with "definite" or "classical" RA initially assigned were prospectively followed for over 5 years. Radiographic cervical findings were classified into three representative instabilities: atlantoaxial subluxation (AAS), vertical subluxation (VS), and subaxial subluxation (SAS). The aggravations of these instabilities were identified in the cases with a decrease of at least 2 mm in the Ranawat value of VS, an increase of at least 1 mm in translation of SAS, or a new development of respective instabilities. RA stages and mutilating changes were assessed in the hand radiograms. RESULTS: Fifty-two point four percent of 267 patients, without any cervical instability at the beginning of follow-up, decreased to 29.6% at the end (P < 0.01), whereas VS and SAS increased significantly (P < 0.01). The aggravation of VS was observed at statistically higher rates in patients with pre-existing instabilities as follows; 25.7% of AAS (P = 0.01), 49.1% of VS (P < 0.01), and 41.2% of SAS (P = 0.06). The aggravation of SAS was also detected in 47.2% of VS and 64.7% of SAS (P < 0.01). Patients with pre-existing mutilating changes exhibited the aggravations of VS and SAS in significantly higher incidences (P < 0.01). Furthermore, the cases with development into mutilating changes during the follow-up showed significantly higher tendencies for the aggravations of these instabilities (P < 0.01). CONCLUSION: The incidences of VS and SAS significantly increased during the minimum 5-year follow-up. Prognostic factors of these instabilities were revealed to be the initial radiological findings of VS, SAS, and mutilating changes.2011年04月, Spine, 36(8) (8), 647 - 53, 英語, 国際誌[査読有り]
- INTRODUCTION: Intervertebral disc tissue homeostasis is modulated by a variety of molecules. Silent mating type information regulator 2 homolog 1 (SIRT1) plays a key role in various physiological processes. The aim of the present study was to verify the expression of SIRT1 and determine SIRT1 function in human intervertebral disc cell homeostasis. METHODS: Human nucleus pulposus (NP) cells were obtained from 24 surgical patients (mean age: 39.4 years) and monolayer-cultured. SIRT1 expression was investigated using RT-PCR analysis and immunohistochemical staining. Quantitative real-time RT-PCR was performed to detect mRNA expression of SIRT1 and other genes: aggrecan, collagen type 2 and Sox9. The effect of SIRT1 on the extracellular matrix metabolism of NP cells was examined using recombinant human SIRT1 protein and a protein delivery reagent. Cell number and proliferation activity were measured following SIRT1 treatment. To reveal the deacetylation potential of transfected recombinant human SIRT1, western blotting for acetylated p53 was utilized. R-phycoerythrin was used for the negative control. RESULTS: SIRT1 expression was confirmed at both mRNA and protein levels in almost all NP cells. Real-time RT-PCR analysis showed SIRT1 mRNA expression significantly increased with donor age (P <0.05, ρ = 0.492). Pfirrmann grade 3 discs showed significantly higher SIRT1 mRNA expression than other grades. SIRT1 treatment significantly reduced aggrecan, Sox9 and collagen type 2 mRNA expression in a dose-dependent manner in all disease classes and disc degeneration grades. Proliferation activity was decreased by SIRT1 treatment in lumbar spinal stenosis and lumbar disc herniation, Pfirrmann grade 3 and grade 4 discs. In contrast, it was significantly upregulated in idiopathic scoliosis, Pfirrmann grade 2 discs. The negative control protein did not affect extracellular matrix metabolism or proliferation activity. CONCLUSIONS: We demonstrate for the first time that SIRT1 is expressed by human NP cells. SIRT1 expression was significantly elevated in an early degeneration stage. SIRT1 affected both extracellular matrix metabolism and proliferation activity; the effect of SIRT1 was altered according to disease class and disc degeneration grade. SIRT1 appears to play a key role in homeostasis during the human intervertebral disc degeneration process.2011年, Arthritis research & therapy, 13(6) (6), R200, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- STUDY DESIGN: Case report. OBJECTIVE: To describe a patient with nodular fasciitis in the sciatic nerve, detected by positron emission tomography (PET). SUMMARY OF BACKGROUND DATA: Severe sciatic pain is commonly caused by lumbar disc herniation, lumbar spinal stenosis, or neoplastic lesion. These lesions are usually diagnosed by plain radiograph, myelography, computed tomography, and magnetic resonance imaging.Nodular fasciitis is a benign connective tissue tumor usually presenting as a firm, rapidly-growing lesion, occasionally arising in the forearm. Only 5 cases of intraneural nodular fasciitis have been reported in the published data, and although some have demonstrated mild neuropathy, none have shown nodular fasciitis with intractable sciatica. METHODS: A 37-year old woman experienced severe sciatica after hitting her left buttock hard on the edge of a bathtub. Physical examination demonstrated intense radiating pain from the left buttock to the lateral calf. There was weakness in the sciatic nerve innervated musculature. She was diagnosed with piriformis syndrome in a local hospital. However, the symptoms remained unchanged after surgery, releasing the piriformis. Conventional imaging of the sciatica including plain radiograph, computed tomography, and magnetic resonance imaging of the spine showed a return of abnormal findings. RESULTS: PET detected an abnormal lesion in the sciatic nerve in the posterior compartment of the patient's left thigh, indicating an intraneural tumor in the sciatic nerve. Subtotal resection was achieved and histologic evaluation of the specimen showed the typical features of nodular fasciitis. After surgery, the patient was relieved of all symptoms, with no evidence of recurrence at the recent 2-year follow-up. CONCLUSION: This is the first reported case of intraneural nodular fasciitis presenting with severe radiculopathy. Nodular fasciitis should be considered in the differential diagnosis of severe sciatica. PET may be a useful tool for diagnosing sciatica of unknown origin that cannot be identified using conventional imaging tools.2010年10月, Spine, 35(21) (21), E1137-40, 英語, 国際誌[査読有り]
- The rodent static compression loading-induced disc degeneration model still has important gaps among the radiographic, magnetic resonance imaging (MRI), and histological schemes and the acute and chronic expression of catabolic genes such as matrix metalloproteinase (MMP)-3. Our objectives were to assess the validity of a rat tail two-disc static compression model and to elucidate a representative catabolic marker, MMP-3 gene alterations, throughout the degenerative process. Static compression at 1.3 MPa for up to 56 days produced progressive disc height loss in radiographs, lower nucleus intensity on T2-weighted MRIs, and histomorphological degeneration. Real-time RT-PCR mRNA quantification showed significant MMP-3 up-regulation in nucleus pulposus cells from 7 days and a significantly progressive increase as the loading duration lengthened, with high correlations to radiological degenerative scores. Immunohistochemistry demonstrated progressively increased positive staining for MMP-3. These results validate this animal model for disc degeneration research. Progressive mRNA and protein-distributional up-regulations indicate the significant role of MMP-3 and its feasibility as a disc degenerative marker. This model should prove useful for investigating the pathomechanism and for evaluating molecular therapies for degenerative disc disease.2010年08月, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 28(8) (8), 1026 - 32, 英語, 国際誌[査読有り]研究論文（学術雑誌）
- We report a case of sudden onset of late infection after TKA inflamed by anti-TNFalpha therapy, Infliximab, in a 54-year-old woman with RA. Infliximab therapy was started 3 years and 8 months after TKAs as a result of multiple arthritides showing high inflammation of RA. One week after the third administration of Infliximab, the patient suffered sudden knee pain and infectious clinical symptoms, and bacteria (MSSA) were detected by joint effusion culture. She was successfully treated by open debridement with antibiotics-loaded calcium phosphate bone paste and cement and the prostheses were retained. Early diagnosis and operative treatment might be the key to controlling infected TKA without removing the implant. This present case might indicate a serious risk of immunosuppressive effects caused by Infliximab.2010年01月, Rheumatology international, 30(3) (3), 405 - 8, 英語, 国際誌[査読有り]
- 日本腰痛学会, 2009年10月, 日本腰痛学会雑誌, 15(1) (1), 99 - 107, 日本語【腰痛疾患に対するinterventional therapy 現在から未来へ】腰痛性疾患に対する分子生物学的治療の可能性[査読有り]
- 日本腰痛学会, 2009年10月, 日本腰痛学会雑誌, 15(1) (1), 199 - 200, 日本語腰痛性疾患に対する分子生物学的アプローチの可能性[査読有り]
- STUDY DESIGN: A case report of the presyrinx state at the craniocervical junction with vanishment of an intramedullary high-signal lesion followed by decompression and fixation. OBJECTIVE: To report the reversible change of an intramedullary high-signal lesion on T2-weighted MRI as a presyrinx state. SUMMARY OF BACKGROUND DATA: The pathology of a T2-weighted high-signal intensity area in the spinal cord has not yet been described in detail. The case presented here showed the vanishment of this lesion after the surgical procedure, which implies that some high-signal intensity lesions might be reversible as a presyrinx state. METHODS: A 75-year-old man presented with severe cervical myelopathy. Neurologic findings and observations on various images indicated compression myelopathy due to both a pseudotumor at the craniocervical junction and spondylosis at C3-C4 disc level due to Klippel-Feil syndrome. The most obvious finding was a vast high-signal intensity lesion at the craniocervical junction, which was speculated to be a syringomyelia before surgery. RESULTS: The MRI at 1 month after surgical treatment (occipito-spinal fusion with the decompression by enlargement of foramen magnum) revealed complete vanishment of the vast high intensity lesion at the craniocervical junction, which remained undetected at the 2 years and 8 months follow-up and corresponded with improvement in the clinical symptoms of myelopathy. CONCLUSION: The vanishment of these signal changes on MRI after surgery was interpreted as a presyrinx state, demonstrating this reversible pathology in the spinal cord.2009年03月, Spine, 34(6) (6), E235-9, 英語, 国際誌[査読有り]
- RNA interference (RNAi) technology has recently emerged as an important biological strategy for gene silencing. Previously, the efficacies of RNAi in cultured nucleus pulposus cells in vitro have been reported. However, RNAi in the disc in vivo has never been reported. Therefore, the aims of the present study were to establish a method for RNAi in the disc in vivo and to evaluate the applicability of this technique for endogenous genes in the intervertebral discs using Fas Ligand (FasL) as a representative endogenous gene. To evaluate the efficacy of RNAi in vivo, two reporter luciferase plasmids (Firefly and Renilla) were used. These plasmids and unmodified short interference RNA (siRNA) duplex for targeting Firefly luciferase were co-transfected into coccygeal intervertebral disc of Sprague-Dawley rats in vivo using the ultrasound gene transfer technique. To evaluate the RNAi of the endogenous gene in vivo, siRNAs targeting rat FasL were transfected with the same technique. Non-specific siRNA was used as the negative control. The discs receiving no siRNAs were used as the control. The inhibitory effect of Firefly luciferase against Renilla luciferase was obtained using the results of dual-luciferase assay. Down-regulation of endogenous FasL was calculated by the data from real-time PCR. Our results showed that siRNA for Firefly luciferase can dramatically down-regulate the Firefly luciferase gene expression in vivo compared with Renilla luciferase. The inhibitory effects were maintained for at least 24 weeks and at 24 weeks post transfection, the inhibitory rate was 80% compared with the control group. Furthermore, the siRNA co-transfection group inhibited endogenous FasL expression by 53% compared with the control group. The present study demonstrates long-term down-regulation mediated by unmodified siRNA is possible not only for the exogenous reporter gene, but also for endogenous FasL expression in rat discs in vivo. This application of RNAi might be promising as a local therapy for disc degeneration and associated disorders by down-regulating some of the genes that are harmful for the normal physiology of the disc and may cause disc degeneration.2009年02月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 18(2) (2), 263 - 70, 英語, 国際誌[査読有り]
- (一社)中部日本整形外科災害外科学会, 2009年01月, 中部日本整形外科災害外科学会雑誌, 52(1) (1), 165 - 166, 日本語ラット椎間板変性モデルを用いた変性過程における遺伝子変動の検討[査読有り]
- Disc degeneration is deeply associated with many spinal disorders and thus has a significant clinical impact on society. The currently available surgical treatment often necessitates removing a pathological disc and spinal fusion. However, it is also well known that these surgical treatments have many potential problems including invasion and cost. Therefore, biological approaches for regenerating these pathological discs have received much attention. Gene therapy is one of these biological approaches. Gene therapy involves the transfer of genes to cells so the recipient cells express these genes and thereby synthesize the RNA and protein they encode in a continuous fashion. One of the significant advantages of gene therapy is that we can expect a lasting duration of biological effect which is potentially beneficial for most disc degeneration associated disorders, as they are, by nature, chronic conditions. Originally, gene therapy was mediated by viral vectors, but recent technological progress has enabled us to opt for non-virus-mediated gene therapy for the disc. Furthermore, the development of the RNA interference technique has enabled us to down-regulate a specific gene expression in the disc opening the door for a new generation of intradiscal gene therapy.2008年12月, European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society, 17 Suppl 4, 459 - 66, 英語, 国際誌[査読有り]
- (株)メディカ出版, 2008年04月, 整形外科看護, 13(4) (4), 372 - 376, 日本語【症状からみる術後合併症 新人ナースのための発見と対応のポイント】牽引・創外固定に伴う合併症 下肢介達牽引中に足関節の背屈ができなくなった[査読有り]
- 日本関節鏡学会, 2008年02月, 関節鏡, 33(1) (1), 73 - 79, 日本語関節鏡視にて診断した異常可動性外側半月(Hypermobile Lateral Meniscus)における臨床所見とMRIの相関性[査読有り]
- (一社)中部日本整形外科災害外科学会, 2007年07月, 中部日本整形外科災害外科学会雑誌, 50(4) (4), 711 - 712, 日本語肘部管症候群の病態と手術成績における電気生理学的検討[査読有り]
- (株)南江堂, 2007年02月, 整形外科, 58(2) (2), 165 - 168, 日本語腫瘍との鑑別を要した慢性腰椎硬膜外血腫の1例[査読有り]
- (一社)中部日本整形外科災害外科学会, 2006年11月, 中部日本整形外科災害外科学会雑誌, 49(6) (6), 1103 - 1104, 日本語大腿骨転子部骨折に対するグライディングネイル法の利点[査読有り]
- 日本関節鏡学会, 2006年07月, 関節鏡, 31(2) (2), 35 - 41, 日本語異常可動性外側半月(Hypermobile Lateral Meniscus)の診断と治療成績[査読有り]
- (株)メジカルビュー社, 2006年05月, 関節外科, 25(5) (5), 561 - 565, 日本語人工股関節全置換術後に肺血栓塞栓症を生じ開心術にて救命しえた1例[査読有り]研究論文（国際会議プロシーディングス）
- (一社)中部日本整形外科災害外科学会, 2006年03月, 中部日本整形外科災害外科学会雑誌, 49(2) (2), 355 - 356, 日本語髄内釘による大腿骨転子部骨折治療時のpitfall カットアウト発生の危険因子[査読有り]
- (社医)愛仁会学術部, 2006年02月, 愛仁会医学研究誌, 37, 64 - 66, 日本語橈骨遠位端骨折を契機に発見された原発性副甲状腺機能亢進症の1例[査読有り]
- (一社)日本自己血輸血学会, 2005年08月, 自己血輸血, 18(1) (1), 16 - 18, 日本語2椎間の後方進入腰椎椎体間固定術における,自己血貯血の必要性についての検討[査読有り]
- (一社)日本自己血輸血学会, 2005年08月, 自己血輸血, 18(1) (1), 19 - 23, 日本語洗浄式自己血回収装置の比較・検討[査読有り]
- (一社)日本自己血輸血学会, 2005年08月, 自己血輸血, 18(1) (1), 37 - 40, 日本語関節リウマチでの人工膝関節全置換術における同種血輸血回避の工夫[査読有り]
- (一社)中部日本整形外科災害外科学会, 2005年07月, 中部日本整形外科災害外科学会雑誌, 48(4) (4), 794 - 795, 日本語Infliximab投与中に人工膝関節遅発性感染を来たした1例[査読有り]
- (一社)日本自己血輸血学会, 2004年12月, 自己血輸血, 17(2) (2), 163 - 165, 日本語単椎間後方進入腰椎椎体間固定術における術中回収式自己血輸血[査読有り]
- 2022年, 整形外科バイオマテリアル研究会プログラム・抄録集, 41st椎間板再生用新規コラーゲン材料の性能評価における実験動物からヒトへの応用展開を指向した力学シミュレーション
- 2021年, 日本整形外科学会雑誌, 95(8) (8)細胞低接着性コラーゲン(low adhesive scaffold collagen:LASCol)を用いた脊椎椎間板組織修復の試み
- 2020年, Journal of Spine Research (Web), 11(3) (3)慢性腰痛症に対する薬物療法の合併症評価(肝腎機能障害を中心に):日本脊椎脊髄病学会主導多施設前向き追跡調査
- (一社)中部日本整形外科災害外科学会, 2019年09月, 中部日本整形外科災害外科学会雑誌, 62(秋季学会) (秋季学会), 186 - 186, 日本語治療に難渋したアテトーゼ型脳性麻痺性頸髄症の1例
- (公社)日本整形外科学会, 2019年09月, 日本整形外科学会雑誌, 93(8) (8), S1883 - S1883, 日本語徐放化抗がん剤局所投与による新たなる骨転移制御の試み
- (公社)日本整形外科学会, 2019年09月, 日本整形外科学会雑誌, 93(8) (8), S1645 - S1645, 日本語腰椎椎間板におけるオートファジー活性は疾患よりも年齢と変性度に依存する
- (公社)日本整形外科学会, 2019年09月, 日本整形外科学会雑誌, 93(8) (8), S1649 - S1649, 日本語ラット脊椎椎間板の恒常性維持におけるAtg5依存性オートファジーの関与
- (公社)日本整形外科学会, 2019年09月, 日本整形外科学会雑誌, 93(8) (8), S1798 - S1798, 日本語腰痛研究最前線:基礎から臨床へ オートファジーの制御による椎間板変性治療の可能性
- (公社)日本整形外科学会, 2019年06月, 日本整形外科学会雑誌, 93(6) (6), S1426 - S1426, 日本語ゼラチンハイドロゲルを用いた徐放化抗がん剤局所投与による骨転移制御
- 日本外科系連合学会, 2019年05月, 日本外科系連合学会誌, 44(3) (3), 534 - 534, 日本語骨転移癌の治療選択-キャンサーボードの運用について- 脊椎転移に対する集学的治療は予後を延長させる
- (公社)日本リハビリテーション医学会, 2019年05月, The Japanese Journal of Rehabilitation Medicine, 56(特別号) (特別号), 3 - 3, 日本語「ロコトレ」理学療法プログラムによる「ロコモ」患者の脊柱アライメントと体幹バランス改善効果
- (公社)日本リハビリテーション医学会, 2019年05月, The Japanese Journal of Rehabilitation Medicine, 56(特別号) (特別号), 3 - 3, 日本語認知機能がロコモ度に及ぼす影響について
- (公社)日本リハビリテーション医学会, 2019年05月, The Japanese Journal of Rehabilitation Medicine, 56(特別号) (特別号), 3 - 14, 日本語「ロコトレ」理学療法プログラムによる「ロコモ」患者の脊柱アライメントと体幹バランス改善効果
- (一社)中部日本整形外科災害外科学会, 2019年03月, 中部日本整形外科災害外科学会雑誌, 62(春季学会) (春季学会), 123 - 123, 日本語70歳以上の脊椎転移患者における手術成績
- (公社)日本整形外科学会, 2019年03月, 日本整形外科学会雑誌, 93(3) (3), S627 - S627, 日本語「ロコトレ」体操による「ロコモ」患者の脊柱アライメントと体幹バランス改善効果
- (公社)日本整形外科学会, 2019年03月, 日本整形外科学会雑誌, 93(3) (3), S1057 - S1057, 日本語70歳以上の脊椎転移患者における手術効果とその経時的推移
- (公社)日本整形外科学会, 2019年03月, 日本整形外科学会雑誌, 93(3) (3), S1073 - S1073, 日本語脊椎転移の症候化リスク因子に関する前向き研究
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 210 - 210, 日本語症候性側彎症手術における電磁気センサー付き椎弓根プローブの有用性
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 268 - 268, 日本語70歳以上の転移性脊椎腫瘍患者における手術成績
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 316 - 316, 日本語術後10年以上に経過観察しえた胸腰椎・腰椎部先天性後側彎症・後彎症における16症例の立位矢状面バランスの検討
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 318 - 318, 日本語筋ジストロフィーに伴う脊柱変形の手術経験
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 348 - 348, 日本語腰椎変性すべり症に対する術後合併椎体間固定術と後方椎体間固定術の手術成績 多施設比較検討
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 406 - 406, 日本語動的圧迫負荷による脊索由来細胞の変化とintegrinα5β1の果たす役割
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 596 - 596, 日本語成人脊柱変形手術において多椎間TLIFとPonte osteotomyのみで十分な腰椎前彎を獲得できるか?
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 609 - 609, 日本語脊椎椎間板におけるオートファジー活性は疾患よりも年齢と変性度に依存する 腰椎椎間板ヘルニア検体と固定術検体との比較
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 644 - 644, 日本語脊椎インスツルメント術後創部感染に対する局所閉鎖陰圧療法の有用性と失敗因子の検討
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 668 - 668, 日本語脊椎転移手術における早期成績不良例に関する検討
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 670 - 670, 日本語骨転移Cancer Boardの効果と課題
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 679 - 679, 日本語mTOR阻害薬テムシロリムスはAktとオートファジーの誘導しヒト椎間板髄核細胞に保護作用を来す
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 702 - 702, 日本語「ロコトレ」リハビリプログラムによる「ロコモ」患者の脊柱アライメントと体幹バランス改善効果
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 269 - 269, 日本語転移性脊椎腫瘍に対する手術加療の費用対効用を低下させる因子の検討
- (一社)日本脊椎脊髄病学会, 2019年03月, Journal of Spine Research, 10(3) (3), 269 - 269, 日本語転移性脊椎腫瘍に対する手術加療の費用対効用を低下させる因子の検討
- (株)メディカルレビュー社, 2018年12月, Anti-aging Science, 10(1) (1), 87 - 87, 日本語エイジングによる骨脆弱化と脊柱変形に対する対策 ロコモ体操による脊柱アライメント改善効果 手術によらない脊柱変形改善の試み
- 日本バイオマテリアル学会, 2018年11月, 日本バイオマテリアル学会大会予稿集, 40回, 216 - 216, 日本語椎間板組織再生のための細胞低接着性コラーゲンゲルの開発
- (一社)日本関節病学会, 2018年10月, 日本関節病学会誌, 37(3) (3), 214 - 214, 日本語関節リウマチの脊椎病変 リウマチ性頸椎不安定性の進行と予後予測因子 10年以上の前向き追跡調査結果
- (公社)日本リハビリテーション医学会, 2018年10月, The Japanese Journal of Rehabilitation Medicine, 55(秋季特別号) (秋季特別号), S299 - S299, 日本語ロコトレリハビリプログラムによる脊柱アライメントと体幹バランスの改善効果
- (公社)日本リハビリテーション医学会, 2018年10月, The Japanese Journal of Rehabilitation Medicine, 55(秋季特別号) (秋季特別号), S274 - S274, 日本語70歳以上の脊椎転移患者の手術成績 PS、ADL、QOLの推移から
- (公社)日本リハビリテーション医学会, 2018年10月, The Japanese Journal of Rehabilitation Medicine, 55(秋季特別号) (秋季特別号), S367 - S367, 日本語脊椎転移の症候化リスク因子の前向き検討
- (一社)中部日本整形外科災害外科学会, 2018年09月, 中部日本整形外科災害外科学会雑誌, 61(秋季学会) (秋季学会), 208 - 208, 日本語脊椎転移に対する手術は予後を延長させる
- (公社)日本整形外科学会, 2018年08月, 日本整形外科学会雑誌, 92(8) (8), S1999 - S1999, 日本語新規低接着性scaffold collagen(LASCol)はラット骨欠損モデルにおいて骨癒合を促進する
- (公社)日本整形外科学会, 2018年08月, 日本整形外科学会雑誌, 92(8) (8), S1733 - S1733, 日本語細胞低接着性コラーゲン(low adhesive scaffold collagen:LASCol)を用いた脊椎椎間板再生の試み
- (公社)日本整形外科学会, 2018年08月, 日本整形外科学会雑誌, 92(8) (8), S1775 - S1775, 日本語動的圧迫負荷が、integrinα5β1を介して脊索由来細胞に与える影響
- (公社)日本整形外科学会, 2018年08月, 日本整形外科学会雑誌, 92(8) (8), S1775 - S1775, 日本語脊椎椎間板におけるオートファジー活性は疾患よりも年齢と変性度に依存する
- (公社)日本整形外科学会, 2018年08月, 日本整形外科学会雑誌, 92(8) (8), S1809 - S1809, 日本語がん骨転移モデルに対するゼラチンハイドロゲルを用いた徐放化抗がん剤局所投与の有効性
- (公社)日本整形外科学会, 2018年08月, 日本整形外科学会雑誌, 92(8) (8), S1881 - S1881, 日本語mTOR阻害薬テムシロリムスがヒト椎間板髄核細胞に及ぼす保護作用はAktとオートファジーの誘導に由来する
- (公社)日本整形外科学会, 2018年06月, 日本整形外科学会雑誌, 92(6) (6), S1512 - S1512, 日本語不安定性を有する転移性脊椎腫瘍に対する治療 脊椎転移に対する手術療法の効果
- (公社)日本リハビリテーション医学会, 2018年05月, The Japanese Journal of Rehabilitation Medicine, 55(特別号) (特別号), 1 - 6, 日本語新規低接着性コラーゲン(LASCol)はラット大腿骨骨欠損モデルにおいて骨癒合を促進する
- (公社)日本リハビリテーション医学会, 2018年05月, The Japanese Journal of Rehabilitation Medicine, 55(特別号) (特別号), 1 - 2, 日本語細胞低接着性コラーゲン(Low Adhesive Scaffold Collagen:LASCol)による脊椎椎間板再生
- (公社)日本整形外科学会, 2018年03月, 日本整形外科学会雑誌, 92(3) (3), S632 - S632, 日本語ロコモティブシンドロームに対するロコモ体操の脊椎・骨盤・下肢矢状断アライメント改善効果
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 429 - 429, 日本語脊椎転移に対する集学的治療は予後を延長させる
- (一社)中部日本整形外科災害外科学会, 2018年03月, 中部日本整形外科災害外科学会雑誌, 61(春季学会) (春季学会), 101 - 101, 日本語前向きコホート研究による症候性脊椎転移の発生リスクに関する検討
- (一社)中部日本整形外科災害外科学会, 2018年03月, 中部日本整形外科災害外科学会雑誌, 61(春季学会) (春季学会), 153 - 153, 日本語Augmented Realityと生体模型により摘出しえた腰部伏針の1例
- (公社)日本整形外科学会, 2018年03月, 日本整形外科学会雑誌, 92(3) (3), S1211 - S1211, 日本語腰椎変性すべり症に対する前後方間接除圧固定術と後方直接除圧固定術の多施設前向き研究による比較検討 臨床成績の観点から
- (公社)日本整形外科学会, 2018年03月, 日本整形外科学会雑誌, 92(3) (3), S1215 - S1215, 日本語腰椎変性すべり症に対する前後合併椎体間固定術と後方椎体間固定術の多施設比較検討 固定椎間のX線学的評価
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 208 - 208, 日本語脊椎疾患治療の費用対効果 脊椎転移に対する手術加療の費用対効用
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 233 - 233, 日本語細胞低接着性コラーゲン(Low Adhesive Scaffold Collagen:LASCol)による脊椎椎間板再生の可能性
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 248 - 248, 日本語腰椎変性すべり症に対するOblique Lateral Interbody Fusion(OLIF)を用いた低侵襲前後合併椎体間固定術と後方椎体間固定術の多施設比較検討
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 289 - 289, 日本語リウマチ頸椎不安定性発生防止のための予測因子 10年以上の前向き多施設共同研究からの検討
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 378 - 378, 日本語ロコモティブシンドロームに関連した脊椎・骨盤・下肢矢状面アライメント障害に対するロコモ体操の改善効果
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 478 - 478, 日本語仙骨骨折を合併した骨盤輪骨折に対するSacral-Aal-Iliac Screwを用いた腰仙椎後側法固定術の有用性
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 537 - 537, 日本語椎間板動的圧迫負荷が脊索由来髄核細胞に及ぼした影響
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 539 - 539, 日本語オートファジーの抑制はヒト椎間板細胞においてアポトーシス・セネッセンスを誘導するが、細胞外基質代謝への影響は少ない
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 540 - 540, 日本語mTORC1阻害薬テムシロリムスのヒト椎間板髄核細胞保護効果はオートファジー及びAktの活性化に由来する
- (一社)日本脊椎脊髄病学会, 2018年03月, Journal of Spine Research, 9(3) (3), 602 - 602, 日本語骨粗鬆に伴う多発椎体骨折を合併した成人脊柱変形手術の特徴と問題点
- (一社)日本移植学会, 2018年02月, 移植, 52(6) (6), 587 - 587, 日本語mTORC1阻害薬テムシロリムスはヒト椎間板髄核細胞の細胞死、細胞老化、細胞外基質分解を抑制する
- 2018年, 多血小板血漿(PRP)療法研究会プログラム・抄録集, 10th細胞低接着性コラーゲン(LASCol)を用いた脊椎椎間板再生の可能性
- (一社)中部日本整形外科災害外科学会, 2017年09月, 中部日本整形外科災害外科学会雑誌, 60(秋季学会) (秋季学会), 143 - 143, 日本語ロコモティブシンドロームに対するロコモ体操の脊椎骨盤矢状面アライメントへの影響
- (公社)日本リハビリテーション医学会, 2017年09月, The Japanese Journal of Rehabilitation Medicine, 54(秋季特別号) (秋季特別号), S339 - S339, 日本語ロコモ体操が脊柱アライメント、重心動揺に与える影響ロコモ体操が脊柱アライメント、重心動揺に与える影響
- (公社)日本整形外科学会, 2017年08月, 日本整形外科学会雑誌, 91(8) (8), S1488 - S1488, 日本語運動器におけるオートファジーとアポトーシス オートファジーの抑制はヒト椎間板細胞においてアポトーシス、セネッセンスを誘導し、細胞数を減少させる
- (公社)日本整形外科学会, 2017年08月, 日本整形外科学会雑誌, 91(8) (8), S1489 - S1489, 日本語運動器におけるオートファジーとアポトーシス 脊椎椎間板変性へのオートファジーの関与とその脊索由来細胞における恒常性維持機構の可能性
- (公社)日本整形外科学会, 2017年08月, 日本整形外科学会雑誌, 91(8) (8), S1691 - S1691, 日本語椎間板変性と再生医療 mTORC1阻害薬テムシロリムスはヒト椎間板髄核細胞において細胞死、細胞老化、細胞外基質分解を抑制する
- (公社)日本整形外科学会, 2017年06月, 日本整形外科学会雑誌, 91(6) (6), S1408 - S1408, 日本語
- (一社)中部日本整形外科災害外科学会, 2017年04月, 中部日本整形外科災害外科学会雑誌, 60(春季学会) (春季学会), 226 - 226, 日本語症候性脊椎転移の発生リスクに関する前向き研究
- (一社)中部日本整形外科災害外科学会, 2017年04月, 中部日本整形外科災害外科学会雑誌, 60(春季学会) (春季学会), 226 - 226, 日本語がん患者の脊椎転移に対する直視下手術と経皮的後方固定術の全身状態、ADL、QOL改善効果
- (一社)中部日本整形外科災害外科学会, 2017年04月, 中部日本整形外科災害外科学会雑誌, 60(春季学会) (春季学会), 227 - 227, 日本語Sepatation surgery後にIMRTを施行した脊椎腫瘍の2例
- (公社)日本整形外科学会, 2017年03月, 日本整形外科学会雑誌, 91(2) (2), S132 - S132, 日本語最重症型骨粗鬆症性多発脊椎椎体骨折に対する後方矯正固定術の臨床成績 2年以上経過症例を対象として
- (公社)日本整形外科学会, 2017年03月, 日本整形外科学会雑誌, 91(2) (2), S471 - S471, 日本語腰椎変性すべり症に対する前後方間接除圧固定術と後方直接除圧固定術の多施設前向き研究による比較検討
- (公社)日本整形外科学会, 2017年03月, 日本整形外科学会雑誌, 91(2) (2), S606 - S606, 日本語がん患者の脊椎転移に対する直視下手術と経皮的後方固定術が及ぼす全身状態、ADL、QOL改善効果の比較
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 296 - 296, 日本語ATG5のノックダウンによるオートファジーの抑制はヒト椎間板細胞のアポトーシスとセネッセンスを誘導し、細胞数を減少させる
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 296 - 296, 日本語ヒト椎間板髄核細胞におけるmTOR阻害薬の細胞死、細胞老化、細胞外基質分解抑止効果の比較
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 322 - 322, 日本語近位端の2椎弓ポリエチレンテープ固定の追加はlong fusionにおけるPJKを予防できるか?
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 485 - 485, 日本語症候性脊椎転移の発生リスクに関する前向き研究
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 504 - 504, 日本語腰椎すべり症に対するOLIFを用いた前後方間接除圧固定術の手術成績 多施設前向き研究による後方直接除圧固定術との比較検討
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 589 - 589, 日本語椎間板髄核におけるオートファジーの重要性とその脊索表現型保持への関与の可能性
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 633 - 633, 日本語神経筋原性側彎症に対する脊椎矯正固定術の治療成績と合併症
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 663 - 663, 日本語がん患者の脊椎転移に対して直視下手術と経皮的後方固定術が全身状態、ADL、QOLに及ぼす影響の比較
- (一社)日本脊椎脊髄病学会, 2017年03月, Journal of Spine Research, 8(3) (3), 779 - 779, 日本語ハイリスク側彎症症例に対する後方側彎症手術の治療成績と周術期合併症
- (公社)日本整形外科学会, 2017年03月, 日本整形外科学会雑誌, 91(2) (2), S179 - S179, 日本語有症状脊椎転移の発生リスクに関する前向き研究
- (一社)中部日本整形外科災害外科学会, 2016年09月, 中部日本整形外科災害外科学会雑誌, 59(秋季学会) (秋季学会), 81 - 81, 日本語DDHと側彎症における小児検診 大都市における側彎症検診の現状と課題
- (一社)中部日本整形外科災害外科学会, 2016年09月, 中部日本整形外科災害外科学会雑誌, 59(秋季学会) (秋季学会), 245 - 245, 日本語脊椎椎間板髄核におけるオートファジーの重要性とその誘導による椎間板変性予防の可能性
- (一社)中部日本整形外科災害外科学会, 2016年09月, 中部日本整形外科災害外科学会雑誌, 59(秋季学会) (秋季学会), 327 - 327, 日本語硬膜内髄外腫瘍に起因する水頭症により意識障害を呈した2例
- (公社)日本整形外科学会, 2016年08月, 日本整形外科学会雑誌, 90(8) (8), S1659 - S1659, 日本語椎間板変性の病態解明 椎間板変性モデルについて
- (公社)日本整形外科学会, 2016年08月, 日本整形外科学会雑誌, 90(8) (8), S1686 - S1686, 日本語脊椎椎間板髄核では他の筋骨格・神経組織よりもオートファジーの関与が大きく、変性が進行するとその活性は減少する
- (公社)日本整形外科学会, 2016年08月, 日本整形外科学会雑誌, 90(8) (8), S1688 - S1688, 日本語mTORシグナル経路への選択的な干渉はオートファジーとAktの活性化を誘導し、ヒト椎間板細胞における細胞死、細胞老化と細胞外基質分解を抑制する 椎間板遺伝子治療の可能性
- (公社)日本整形外科学会, 2016年06月, 日本整形外科学会雑誌, 90(6) (6), S1286 - S1286, 日本語
- (公社)日本整形外科学会, 2016年03月, 日本整形外科学会雑誌, 90(2) (2), S94 - S94, 日本語脊椎転移に対する集学的治療の予後改善効果
- (公社)日本整形外科学会, 2016年03月, 日本整形外科学会雑誌, 90(2) (2), S183 - S183, 日本語脊椎転移に対する手術加療の費用対効用
- (公社)日本整形外科学会, 2016年03月, 日本整形外科学会雑誌, 90(2) (2), S241 - S241, 日本語リウマチ頸椎不安定性重症化の予測因子 外来通院患者を対象とした10年以上の多施設共同前向き追跡調査からの検討
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 196 - 196, 日本語脊椎転移に対する集学的治療の予後改善効果
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 384 - 384, 日本語mTORシグナル経路への選択的な干渉はオートファジーとAktの活性化を誘導し、ヒト椎間板細胞における細胞死、老化と細胞外基質分解を抑制する
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 451 - 451, 日本語Adiponectinの椎間板細胞に対する抗炎症効果と椎間板変性に伴うAdiponectin受容体の発現変化
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 453 - 453, 日本語椎間板では他の筋骨格系組織よりもオートファジーの関与が大きく、その活性は変性とともに減少する オートファジー制御による椎間板変性予防の可能性
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 461 - 461, 日本語骨粗鬆症性椎体骨折偽関節に対する手術戦略の検討
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 469 - 469, 日本語重度症候性側彎症手術時の椎弓根スクリュー刺入における電磁気センサー付きプローブの有用性
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 478 - 478, 日本語骨粗鬆症性多発脊椎椎体骨折に対する後方矯正固定術の臨床成績 1年以上経過症例を対象として
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 605 - 605, 日本語腰椎すべり症に対するOblique Lateral Interbody Fusion(OLIF)を用いた低侵襲前方後方固定術の手術成績 後方椎体間固定術との比較検討
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 700 - 700, 日本語がん患者の脊椎転移に対する経皮的後方固定術の全身状態、ADL、QOL改善効果 直視下手術と比較して
- (一社)日本脊椎脊髄病学会, 2016年03月, Journal of Spine Research, 7(3) (3), 709 - 709, 日本語脊髄円錐レベル近傍の硬膜内髄外腫瘍の特徴と問題点
- 日本脊椎脊髄病学会, 2016年02月, Journal of spine research : official journal of the Japanese Society for Spine Surgery and Related Research, 7(2) (2), 114 - 121, 英語Predictive Risk Factors for Severe Aggravation of Cervical Spine Instabilities in Rheumatoid Arthritis : A Prospective, Multicenter Over 10-year Cohort Study of Outpatients (日本脊椎脊髄病学会 英文原著号) -- (Excellent Papers of the 44th Annual Meeting of The Japanese Society for Spine Surgery and Related Research)
- (一社)日本関節病学会, 2015年10月, 日本関節病学会誌, 34(3) (3), 482 - 482, 日本語関節リウマチの脊椎病変 病態と手術治療 リウマチ頸椎不安定性の重症化予測因子
- (公社)日本整形外科学会, 2015年09月, 日本整形外科学会雑誌, 89(8) (8), S1610 - S1610, 日本語椎間板細胞に対するadiponectinの抗炎症効果
- (一社)中部日本整形外科災害外科学会, 2015年09月, 中部日本整形外科災害外科学会雑誌, 58(秋季学会) (秋季学会), 110 - 110, 日本語骨粗鬆症性椎体破裂骨折に対する手術戦略の検討
- (一社)中部日本整形外科災害外科学会, 2015年09月, 中部日本整形外科災害外科学会雑誌, 58(秋季学会) (秋季学会), 142 - 142, 日本語重度症候性側彎症例への椎弓根スクリュー刺入における電磁波センサー付きプローブの有用性
- (一社)中部日本整形外科災害外科学会, 2015年09月, 中部日本整形外科災害外科学会雑誌, 58(秋季学会) (秋季学会), 287 - 287, 日本語高悪性度脊椎転移に対する手術成績
- (公社)日本整形外科学会, 2015年09月, 日本整形外科学会雑誌, 89(8) (8), S1522 - S1522, 日本語椎間板変性メカニズムと再生への架け橋 椎間板変性と抗老化因子との関係について
- (公社)日本整形外科学会, 2015年09月, 日本整形外科学会雑誌, 89(8) (8), S1613 - S1613, 日本語mTORシグナル経路への選択的な干渉は椎間板における細胞死、老化と細胞外基質分解を抑制する
- (公社)日本整形外科学会, 2015年09月, 日本整形外科学会雑誌, 89(8) (8), S1613 - S1613, 日本語ラパマイシン以外のmTOR阻害薬は椎間板細胞におけるアポトーシス、セネッセンス、細胞外基質分解を抑制しない
- (公社)日本整形外科学会, 2015年09月, 日本整形外科学会雑誌, 89(8) (8), S1614 - S1614, 日本語ラパマイシンの椎間板細胞保護作用はオートファジーの誘導だけでなくAkt活性の上昇に由来している
- (公社)日本整形外科学会, 2015年06月, 日本整形外科学会雑誌, 89(6) (6), S1355 - S1355, 日本語
- (一社)中部日本整形外科災害外科学会, 2015年05月, 中部日本整形外科災害外科学会雑誌, 58(3) (3), 609 - 609, 日本語椎体全摘出術後に側彎症手術を要した第3腰椎骨芽細胞腫の1例
- (公社)日本整形外科学会, 2015年03月, 日本整形外科学会雑誌, 89(2) (2), S363 - S363, 日本語関節リウマチ脊椎病変の疫学および治療戦略の変化 関節リウマチ頸椎病変の疫学と自然経過
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 237 - 237, 日本語骨粗鬆症性多発椎体骨折に伴う矢状面インバランスに対する手術戦略と問題点
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 244 - 244, 日本語RA環軸関節前方亜脱臼に対する環軸関節固定術の意義 自然経過例との比較検討
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 244 - 244, 日本語リウマチ頸椎不安定性の重症化予測因子 外来通院患者を対象とした10年以上の多施設共同前向き追跡調査からの検討
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 295 - 295, 日本語80歳以上の高齢者患者の脊椎術後合併症の検討
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 416 - 416, 日本語外来通院患者のリウマチ頸椎不安定性重症化の推移 10年以上の前向き多施設共同研究からの検討
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 589 - 589, 日本語椎間板細胞に対するadiponectinの抗炎症効果に関する検討
- (公社)日本整形外科学会, 2015年03月, 日本整形外科学会雑誌, 89(3) (3), S974 - S974, 日本語重症症候性側彎症例における電磁波センサー付きプローブを用いた椎弓根スクリュー刺入法の有用性
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 486 - 486, 日本語EuroQOL-5D(EQ-5D)を用いた転移性脊椎腫瘍に対する手術加療の費用対効用
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 518 - 518, 日本語高齢者脊椎転移に対する手術成績
- (一社)日本脊椎脊髄病学会, 2015年03月, Journal of Spine Research, 6(3) (3), 640 - 640, 日本語骨転移専門tumor boardの取り組み
- (公社)日本整形外科学会, 2015年03月, 日本整形外科学会雑誌, 89(3) (3), S667 - S667, 日本語
- (一社)日本関節病学会, 2014年10月, 日本関節病学会誌, 33(3) (3), 361 - 361, 日本語関節リウマチに対する頸椎手術の進歩 RA頸椎病変の自然経過と手術適応
- (公社)日本整形外科学会, 2014年08月, 日本整形外科学会雑誌, 88(8) (8), S1401 - S1401, 日本語オートファジーと整形外科疾患 栄養の欠乏は椎間板細胞におけるオートファジー、アポトーシス、セネッセンスならびに細胞外基質代謝に関与する
- (公社)日本整形外科学会, 2014年08月, 日本整形外科学会雑誌, 88(8) (8), S1519 - S1519, 日本語クロロキンは椎間板細胞においてオートファジーを阻害するとともにアポトーシスとセネッセンスを誘導し細胞外基質分解を促進する
- (公社)日本整形外科学会, 2014年08月, 日本整形外科学会雑誌, 88(8) (8), S1520 - S1520, 日本語外因性SIRT1はヒト変性椎間板髄核細胞のオートファジーを亢進しアポトーシスを抑制する
- (公社)日本整形外科学会, 2014年08月, 日本整形外科学会雑誌, 88(8) (8), S1571 - S1571, 日本語椎間板の変性・再生 椎間板変性の機序とそれに準じた再生の可能性
- (公社)日本整形外科学会, 2014年08月, 日本整形外科学会雑誌, 88(8) (8), S1695 - S1695, 日本語動的圧迫負荷による脊索由来椎間板髄核細胞の変化
- (公社)日本整形外科学会, 2014年08月, 日本整形外科学会雑誌, 88(8) (8), S1521 - S1521, 日本語椎間板細胞に対するadiponectinの抗炎症効果
- (一社)日本移植学会, 2014年05月, 移植, 49(1) (1), 174 - 174, 日本語動的圧迫負荷による椎間板変性にintegrin α5β1メカノレセプターが及ぼす影響
- (一社)日本脊椎脊髄病学会, 2014年03月, Journal of Spine Research, 5(3) (3), 238 - 238, 日本語外因性SIRT1は低栄養条件下においてオートファジーを介しヒト椎間板髄核細胞のアポトーシスを阻害する
- (一社)日本脊椎脊髄病学会, 2014年03月, Journal of Spine Research, 5(3) (3), 541 - 541, 日本語椎間板動的圧迫負荷による脊索由来髄核細胞の変化
- (公社)日本整形外科学会, 2014年03月, 日本整形外科学会雑誌, 88(2) (2), S438 - S438, 日本語リウマチ性頸椎病変に対する治療戦略 RA頸椎病変の自然経過
- (一社)日本脊椎脊髄病学会, 2014年03月, Journal of Spine Research, 5(3) (3), 208 - 208, 日本語10年間におけるRA頸椎不安定性の進行 外来通院患者の前向き多施設共同研究
- (一社)日本脊椎脊髄病学会, 2014年03月, Journal of Spine Research, 5(3) (3), 238 - 238, 日本語脊椎変性疾患の変性椎間板にはM1マクロファージが存在する
- (公社)日本整形外科学会, 2013年08月, 日本整形外科学会雑誌, 87(8) (8), S1632 - S1632, 日本語椎間板動的圧迫負荷による脊索由来髄核細胞の変化
- (公社)日本整形外科学会, 2013年08月, 日本整形外科学会雑誌, 87(8) (8), S1456 - S1456, 日本語SIRT1は低栄養条件下においてヒト椎間板髄核細胞のオートファジーを介しアポトーシスを抑制する会議報告等
- (一社)日本脊椎脊髄病学会, 2013年03月, Journal of Spine Research, 4(3) (3), 409 - 409, 日本語非ヘルニア変性椎間板には古典的活性化(M1)マクロファージが存在する
- (公社)日本整形外科学会, 2013年03月, 日本整形外科学会雑誌, 87(2) (2), S356 - S356, 日本語腰椎椎間板vacuum現象の分類の試みと臨床的意義について会議報告等
- (一社)日本脊椎脊髄病学会, 2013年03月, Journal of Spine Research, 4(3) (3), 301 - 301, 日本語椎間板変性では脊索由来細胞の消失が細胞外基質の分解を惹起する ラット椎間板多段階変性モデルにおける検討会議報告等
- (一社)中部日本整形外科災害外科学会, 2013年03月, 中部日本整形外科災害外科学会雑誌, 56(春季学会) (春季学会), 126 - 126, 日本語椎間板変性では脊索由来細胞の消失を契機として細胞外基質分解が進行する ラット椎間板変性モデルでの検討会議報告等
- (公社)日本整形外科学会, 2013年03月, 日本整形外科学会雑誌, 87(2) (2), S240 - S240, 日本語動的圧迫負荷による椎間板変性にintegrin α5β1が関与している会議報告等
- (一社)日本脊椎脊髄病学会, 2013年03月, Journal of Spine Research, 4(3) (3), 408 - 408, 日本語外因性SIRT1は低栄養条件下においてオートファジーを介しヒト椎間板髄核細胞の細胞増殖能を活性化させる会議報告等
- (一社)日本脊椎脊髄病学会, 2013年03月, Journal of Spine Research, 4(3) (3), 410 - 410, 日本語共培養モデルを用いた椎間板ヘルニアにおける疼痛発生機序の検討会議報告等
- (一社)日本脊椎脊髄病学会, 2013年03月, Journal of Spine Research, 4(3) (3), 804 - 804, 日本語腰椎椎間板vacuum現象のCT矢状断再構成像を用いた分類の試み会議報告等
- (公社)日本整形外科学会, 2012年08月, 日本整形外科学会雑誌, 86(8) (8), S1121 - S1121, 日本語ラット椎間板多段階変性モデルにおいて細胞外基質の分解は脊索由来細胞の消失と相関している
- (公社)日本整形外科学会, 2012年08月, 日本整形外科学会雑誌, 86(8) (8), S1128 - S1128, 日本語低栄養条件や疑似的低酸素条件下において長寿因子SIRT1が椎間板細胞のオートファジー活性に与える影響についての検討
- (公社)日本整形外科学会, 2012年08月, 日本整形外科学会雑誌, 86(8) (8), S1397 - S1397, 日本語動的圧迫負荷が椎間板細胞のメカノレセプター発現に及ぼした影響
- (一社)日本脊椎脊髄病学会, 2012年03月, Journal of Spine Research, 3(3) (3), 268 - 268, 日本語椎間板変性の初期にはADAMTS-5の発現が、進行期から末期にはMMP-3の発現が増大している ラット尾椎椎間板多段階圧迫モデルにおける検討
- (一社)日本脊椎脊髄病学会, 2012年03月, Journal of Spine Research, 3(3) (3), 283 - 283, 日本語重度RA頸椎病変に対する術式変更の効用 多椎間後方固定術の意義
- (一社)日本脊椎脊髄病学会, 2012年03月, Journal of Spine Research, 3(3) (3), 504 - 504, 日本語椎間板ヘルニアモデルにおいて抗IL-8抗体と抗TNFalpha抗体の両者の投与により疼痛域値が改善する
- (一社)日本脊椎脊髄病学会, 2012年03月, Journal of Spine Research, 3(3) (3), 505 - 505, 日本語椎間板ヘルニアにおける炎症性反応には髄核細胞に発現するFas ligandが関与する 椎間板ヘルニアの疼痛発生機序解明に向けて
- (一社)日本脊椎脊髄病学会, 2012年03月, Journal of Spine Research, 3(3) (3), 507 - 507, 日本語動的圧迫負荷がラット椎間板に及ぼす影響
- (一社)日本リウマチ学会, 2012年03月, 日本リウマチ学会総会・学術集会・国際リウマチシンポジウムプログラム・抄録集, 56回・21回, 172 - 172, 日本語リウマチ頸椎病変は今 RA頸椎病変の進行
- (公社)日本整形外科学会, 2012年02月, 日本整形外科学会雑誌, 86(2) (2), S52 - S52, 日本語マクロファージと椎間板の相互作用によるTNFalpha、IL-6、IL-8、PGE2産生が椎間板ヘルニアの炎症性痛に関与している
- (公社)日本整形外科学会, 2011年08月, 日本整形外科学会雑誌, 85(8) (8), S1148 - S1148, 日本語ヒト椎間板髄核細胞においてFas ligandは炎症性サイトカイン産生に関与する 椎間板ヘルニアにおける疼痛発生機序の解明に向けて
- (公社)日本整形外科学会, 2011年08月, 日本整形外科学会雑誌, 85(8) (8), S1243 - S1243, 日本語圧負荷を解除することで多様な変性段階の再現を可能にした
- (一社)中部日本整形外科災害外科学会, 2011年03月, 中部日本整形外科災害外科学会雑誌, 54(春季学会) (春季学会), 93 - 93, 日本語JOACMEQを用いた頸部脊髄症の手術適応基準作成の試み
- (一社)日本脊椎脊髄病学会, 2011年03月, Journal of Spine Research, 2(3) (3), 487 - 487, 日本語腰部脊柱管狭窄症に対する最小侵襲手術を目的とした腰椎棘突起間スペーサーの開発 ヒト屍体と大型動物を用いた前臨床研究
- (一社)日本脊椎脊髄病学会, 2011年03月, Journal of Spine Research, 2(3) (3), 520 - 520, 日本語脊髄神経鞘腫の摘出に伴う神経脱落症状の出現頻度
- (一社)日本脊椎脊髄病学会, 2011年03月, Journal of Spine Research, 2(3) (3), 560 - 560, 日本語新JOA評価法の現況と展望 JOACMEQを用いた頸部脊髄症の手術適応基準作成の試み
- (一社)日本脊椎脊髄病学会, 2011年03月, Journal of Spine Research, 2(3) (3), 593 - 593, 日本語頸椎疾患手術の適応と問題点 頸髄症に対する単純MRI、Kinematic MRI、Myelographyを用いた狭窄高位の評価 Myelographyは必要か?
- (公社)日本整形外科学会, 2011年02月, 日本整形外科学会雑誌, 85(2) (2), S74 - S74, 日本語腰部脊柱管狭窄症に対する最小侵襲手術を目的とした腰椎棘突起間スペーサーの開発 ヒト死体と大型動物を用いた前臨床研究
- (公社)日本整形外科学会, 2011年02月, 日本整形外科学会雑誌, 85(2) (2), S110 - S110, 日本語細胞生物学的な椎間板変性指標の確立を目指して ラット椎間板変性モデルを用いた検討
- (公社)日本整形外科学会, 2011年02月, 日本整形外科学会雑誌, 85(2) (2), S202 - S202, 日本語リウマチ頸椎病変 手術は、いつ、誰に必要なのか 近年発展を遂げた分野 RA頸椎病変における手術適応と術式選択 病変進行の観点から
- (公社)日本整形外科学会, 2010年08月, 日本整形外科学会雑誌, 84(8) (8), S1252 - S1252, 日本語長寿因子Sirt1がヒト椎間板髄核細胞の細胞活性に与える影響の検討
- (公社)日本整形外科学会, 2010年08月, 日本整形外科学会雑誌, 84(8) (8), S1259 - S1259, 日本語ラット尾椎椎間板静的圧迫モデルを用いた椎間板変性におけるアポトーシス機序の検討
- (一社)中部日本整形外科災害外科学会, 2010年05月, 中部日本整形外科災害外科学会雑誌, 53(3) (3), 709 - 709, 日本語脊椎硬膜外膿瘍と鑑別を要した広範囲転移性脊椎硬膜外腫瘍の1例
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S272 - S272, 日本語頸椎症性脊髄症と後縦靱帯骨化症の術後成績の比較 JOACMEQによる評価
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S367 - S367, 日本語気孔率の異なる2種類のハイドロキシアパタイト製スペーサーに対する骨結合能の評価 前向き研究
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S396 - S396, 日本語頸椎椎弓形成術術後の臨床症状の経時的変化 JOACMEQによる前向き研究
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S409 - S409, 日本語日本整形外科学会腰痛評価質問票(JOABPEQ)を用いた腰椎後方手術の経時的臨床評価
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S410 - S410, 日本語腰部脊柱管狭窄症において症状が発現する立位と軽快する座位の違いはなにか 形態機能的解析
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S686 - S686, 日本語一般診療医に腰部脊柱管狭窄症の認識度を高めるための前向き研究
- (公社)日本整形外科学会, 2010年04月, 日本整形外科学会雑誌, 84(4) (4), S716 - S716, 日本語リウマチ性(RA)頸椎不安定性における増悪予測因子の検討
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 377 - 377, 日本語JOA新評価基準 臨床応用の展開 頸椎椎弓形成術術後の臨床症状の経時的変化 JOACMEQによる前向き研究
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 399 - 399, 日本語長寿因子Sirt1のヒト椎間板髄核細胞における発現と細胞活性に与える影響の検討
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 435 - 435, 日本語腰部脊柱管狭窄症に対する術式別(固定術VS開窓術)の経時的臨床評価
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 497 - 497, 日本語腰部脊柱管狭窄症に対する最小侵襲手術を目的とした腰椎棘突起間スペーサーの開発
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 529 - 529, 日本語RA頸椎不安定性の発生とその重症化 不安定性を認めない症例に対する前向き追跡調査
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 557 - 557, 日本語腰部脊柱管狭窄症の症状発現に関する姿勢性因子の関与 症状が増悪する立位と軽快する座位における責任椎間の動きについて
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 666 - 666, 日本語ラット尾椎椎間板圧迫モデルを用いた椎間板変性におけるアポトーシス機序の解明
- (一社)日本脊椎脊髄病学会, 2010年03月, Journal of Spine Research, 1(3) (3), 699 - 699, 日本語高齢者頸髄症に対する頸椎椎弓形成術の術後成績 JOACMEQによる評価
- (公社)日本整形外科学会, 2010年03月, 日本整形外科学会雑誌, 84(3) (3), S124 - S124, 日本語高齢者頸髄症に対する頸椎椎弓形成術の術後成績 JOA点数とJOACMEQによる評価の差
- (公社)日本整形外科学会, 2010年03月, 日本整形外科学会雑誌, 84(3) (3), S126 - S126, 日本語棘突起縦割式脊柱管拡大術における項靱帯温存手術の意義 Randomized controlled trial
- 2009年11月30日, 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 20(3) (3), 692 - 695, 英語Evaluation of Clinical Outcomes of C3-6 Laminoplasty compared with Conventional C3-7 Laminoplasty using the JOACMEQ Scoring System
- 2009年11月30日, 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 20(3) (3), 713 - 717, 英語A Prospective Clinical Evaluation of the Posterior Lumbar Surgery in Our Hospital using the JOA Back Pain Evaluation Questionnaire (JOABPEQ)
- (一社)中部日本整形外科災害外科学会, 2009年09月, 中部日本整形外科災害外科学会雑誌, 52(秋季学会) (秋季学会), 38 - 38, 日本語腰部脊柱管狭窄症に対する最小侵襲手術をめざした棘突起間スペーサーの開発 Why not IPD?
- (公社)日本整形外科学会, 2009年08月, 日本整形外科学会雑誌, 83(8) (8), S1162 - S1162, 日本語慢性疼痛(腰部)の発現機序 椎間板性腰痛の発現機序 免疫学的な観点から
- (公社)日本整形外科学会, 2009年08月, 日本整形外科学会雑誌, 83(8) (8), S1203 - S1203, 日本語経皮的に挿入・抜去が可能な腰椎棘突起間スペーサーの開発 腰部脊柱管狭窄症に対する最小侵襲手術をめざして
- (公社)日本整形外科学会, 2009年08月, 日本整形外科学会雑誌, 83(8) (8), S1208 - S1208, 日本語長寿因子Sirt 1のヒト椎間板髄核細胞における発現の検討
- (公社)日本整形外科学会, 2009年08月, 日本整形外科学会雑誌, 83(8) (8), S1210 - S1210, 日本語基質代謝関連遺伝子の発現変動からみた椎間板変性の機序 ラット椎間板静的圧迫モデルを用いた長期の検討
- (公社)日本整形外科学会, 2009年06月, 日本整形外科学会雑誌, 83(6) (6), S964 - S964, 日本語激烈な坐骨神経痛を呈しPETにより検出しえた坐骨神経内結節性筋膜炎の1例
- (一社)日本脊椎脊髄病学会, 2009年03月, 日本脊椎脊髄病学会雑誌, 20(1) (1), 11 - 11, 日本語頸椎椎弓形成術におけるC7項靱帯付着部温存の意義 JOACMEQによる評価
- (一社)日本脊椎脊髄病学会, 2009年03月, 日本脊椎脊髄病学会雑誌, 20(1) (1), 18 - 18, 日本語当院における腰椎後方手術の経時的臨床評価 日本整形外科学会腰痛評価質問票(JOABPEQ)を用いて
- (一社)日本脊椎脊髄病学会, 2009年03月, 日本脊椎脊髄病学会雑誌, 20(1) (1), 70 - 70, 日本語頸椎椎弓形成術における後方支持組織の役割 Randomized Controlled Trial(RCT)
- (一社)日本脊椎脊髄病学会, 2009年03月, 日本脊椎脊髄病学会雑誌, 20(1) (1), 105 - 105, 日本語持続的な圧負荷は椎間板髄核における異化・同化遺伝子群の不均衡を経時的に増大させる ラット尾椎椎間板変性モデルを用いた椎間板変性機序の解明
- (一社)日本脊椎脊髄病学会, 2009年03月, 日本脊椎脊髄病学会雑誌, 20(1) (1), 308 - 308, 日本語ハイドロキシアパタイト製スペーサーの骨結合率はハイドロシキシアパタイトの気孔率に依存する A randomized controlled clinical trial
- (一社)日本脊椎脊髄病学会, 2009年03月, 日本脊椎脊髄病学会雑誌, 20(2) (2), 324 - 324, 日本語RA頸椎不安定性の追跡調査結果 外来通院患者5年間の前向き多施設共同研究
- (公社)日本整形外科学会, 2009年03月, 日本整形外科学会雑誌, 83(3) (3), S518 - S518, 日本語ハイドロキシアパタイトの骨結合に対する前向き調査 A randomized controlled clinical trial
- (公社)日本整形外科学会, 2009年03月, 日本整形外科学会雑誌, 83(3) (3), S557 - S557, 日本語プライマリー医における腰部脊柱管狭窄の認識度とサポートツールの有用性に関するアンケート調査
- (一社)中部日本整形外科災害外科学会, 2009年03月, 中部日本整形外科災害外科学会雑誌, 52(2) (2), 513 - 513, 日本語診断に難渋した左下肢痛の1例
- (公社)日本整形外科学会, 2009年02月, 日本整形外科学会雑誌, 83(2) (2), S77 - S77, 日本語頸椎椎弓形成術ではC7項靱帯付着部温存は頸椎機能の保持に有用であるJOACMEQによる評価
- (一社)中部日本整形外科災害外科学会, 2008年09月, 中部日本整形外科災害外科学会雑誌, 51(秋季学会) (秋季学会), 100 - 100, 日本語ラット椎間板変性モデルを用いた変性過程における遺伝子変動の検討 椎間板変性機序の解明を目指して
- (一社)中部日本整形外科災害外科学会, 2008年09月, 中部日本整形外科災害外科学会雑誌, 51(秋季学会) (秋季学会), 162 - 162, 日本語強直性脊椎骨増殖症による強直部位での骨折のために遅発性麻痺を生じた3例
- (公社)日本整形外科学会, 2007年06月, 日本整形外科学会雑誌, 81(6) (6), S797 - S797, 日本語砂時計腫として仙骨に発生したRhabdoid Meningiomaの1例
- (一社)日本脊椎脊髄病学会, 2007年03月, 日本脊椎脊髄病学会雑誌, 18(2) (2), 353 - 353, 日本語頸椎MRIは全ての脊髄圧迫病態を描出できるのか 脊髄造影との比較検討
- (一社)日本脊椎脊髄病学会, 2007年03月, 日本脊椎脊髄病学会雑誌, 18(2) (2), 363 - 363, 日本語RAに対する後頭脊椎固定術の術後成績 long fusionとshort fusionの比較
- (一社)中部日本整形外科災害外科学会, 2007年03月, 中部日本整形外科災害外科学会雑誌, 50(春季学会) (春季学会), 101 - 101, 日本語肘部管症候群の病態と手術成績における電気生理学的検討
- (一社)中部日本整形外科災害外科学会, 2007年01月, 中部日本整形外科災害外科学会雑誌, 50(1) (1), 176 - 176, 日本語MRI T2強調画像髄内高輝度変化が術後完全に消失したKlippel-Feil症候群の1例
- 日本最小侵襲整形外科学会, 2006年09月, 日本最小侵襲整形外科学会誌, 6(1) (1), 35 - 35, 日本語大腿骨転子部骨折に対する最小侵襲髄内釘手術
- (一社)日本骨折治療学会, 2006年06月, 骨折, 28(Suppl.) (Suppl.), S141 - S141, 日本語大腿骨頸部内側に対するdual SC screw
- (一社)日本骨折治療学会, 2006年06月, 骨折, 28(Suppl.) (Suppl.), S146 - S146, 日本語大腿骨転子部骨折に対する髄内釘手術時の工夫 改良式大腿骨軸マーキング法
- 日本関節鏡学会, 2006年06月, 関節鏡, 31(1) (1), 133 - 133, 日本語異常可動性外側半月(hypermobile lateral meniscus)における臨床所見とMRIの相関性
- 日本関節鏡学会, 2006年06月, 関節鏡, 31(1) (1), 205 - 205, 日本語関節鏡視下半月切除後に生じた骨壊死例の検討
- (一社)中部日本整形外科災害外科学会, 2005年03月, 中部日本整形外科災害外科学会雑誌, 48(2) (2), 406 - 406, 日本語腫瘍と鑑別を要した慢性腰椎硬膜外血腫の1例
- (一社)日本自己血輸血学会, 2005年02月, 自己血輸血, 18(学術総会) (学術総会), S17 - S17, 日本語関節リウマチ患者の自己血輸血の工夫 関節リウマチ(RA)患者での人工膝関節全置換術(TKA)における自己血輸血及びトラネキサム酸を用いた同種血輸血回避の工夫
- (一社)日本自己血輸血学会, 2005年02月, 自己血輸血, 18(学術総会) (学術総会), S25 - S25, 日本語2椎間の後方進入腰椎椎体間固定術における,自己血貯血の必要性についての検討
- (一社)日本自己血輸血学会, 2005年02月, 自己血輸血, 18(学術総会) (学術総会), S25 - S25, 日本語洗浄式自己血回収装置の比較,検討
- (一社)中部日本整形外科災害外科学会, 2003年11月, 中部日本整形外科災害外科学会雑誌, 46(6) (6), 1177 - 1177, 日本語THA(人工股関節全置換術)後に肺血栓塞栓症を生じ開心術にて救命し得た1例
- 共編者(共編著者), 22(20), 11012; 22(21), 11355; 22(23), 12875; 22(24), 13641; 23(1), 371; 23(5), 2530; 23(5), 2721; 23(6), 2973; 23(7), 4014; 23(7), 4059; 23(8), 4267; 23(9), 5038; 23(11), 6218; 23(13), 7306; 23(17), 9710, Multidisciplinary Digital Publishing Institute, 2022年08月International Journal of Molecular Sciences
- 共編者(共編著者), 22(4-16), 1744; 2579; 3519; 3638; 3965; 4141; 4248; 4453; 4723; 4853; 4917; 5281; 5648; 6015; 6970; 8356, Multidisciplinary Digital Publishing Institute, 2021年08月International Journal of Molecular Sciences
- Seminar for Safe Cervical Spine Surgery 2023, 2023年03月中下位頚椎後方手術：Instrumentation[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第24回圧迫性脊髄症研究会, 2023年03月頚胸椎後方除圧術後に生じた浸出液産生浮遊性血腫の一例[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第13回日本成人脊柱変形学会, 2023年03月重症骨粗鬆症患者のlong fusionで近位端でのポリエチレンテープの使用はPJKに伴う再手術を抑制する口頭発表（一般）
- 第13回日本成人脊柱変形学会, 2023年03月ロコトレ通院リハビリテーションによるロコモ患者の脊柱アライメント改善効果：2年以上の前向き追跡調査口頭発表（一般）
- 第13回日本成人脊柱変形学会, 2023年03月体幹コルセット採型における石膏包帯使用時と3Dデジタルスキャナ使用時の比較検討口頭発表（一般）
- The 13th Cervical Spine Research Society Asia Pacific Section, 2023年03月Surgical outcomes and predictive risk factors for cervical spine metastasis: a prospective study of 46 cases口頭発表（一般）
- 第59回脊椎外科を学ぶ会, 2023年03月脳脊髄液漏出症に脳表ヘモジデリン沈着症を合併した1例口頭発表（一般）
- 第35回日本軟骨代謝学会, 2023年03月ラット椎間板恒常性維持へのオートファジーの関与：Atg5に対するRNA干渉を用いた細胞・動物実験による検討[招待有り]口頭発表（招待・特別）
- 第35回日本軟骨代謝学会, 2023年03月CRISPR-Cas9システムとRNA干渉法を用いたmTORシグナル経路の選択的阻害による脊椎椎間板変性治療効果の比較ポスター発表
- The 69th Annual Meeting, Orthopaedic Research Society, 2023年02月Transient Receptor Potential Vanilloid 4 (TRPV4) knockdown decreases extracellular matrix synthesis via autophagy suppression in rat intervertebral disc口頭発表（一般）
- The 69th Annual Meeting, Orthopaedic Research Society, 2023年02月Development of treatment for degenerative disc disease by the selective gene silencing of mTOR signaling using the RNA interference and CRISPR–Cas9 systemsポスター発表
- The 69th Annual Meeting, Orthopaedic Research SocietyThe efficacy of Adiponectin receptor agonist AdipoRon against intervertebral disc degeneration on rat tail puncture modeポスター発表
- 第18回兵庫県転移性骨腫瘍治療研究会, 2023年02月脊椎転移手術における合併症発生リスク因子に関する研究口頭発表（一般）
- 久光製薬株式会社医薬情報担当者教育研修会, 2023年01月難治性疼痛・神経痛を有する脊椎疾患の治療戦略～ジクロフェナクナトリウム経皮吸収型持続性疼痛治療剤への期待～[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第5回脊椎腫瘍・骨粗鬆症研究会, 2022年12月診断に難渋した視神経脊髄炎の1例口頭発表（一般）
- “痛み”の治療を考える会, 2022年11月脊椎疾患の治療で難渋する神経障害性疼痛の診断と治療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第56回脊椎外科を学ぶ会, 2022年11月頸椎症性脊髄症術後1ヶ月で硬膜外血腫が生じた２例口頭発表（一般）
- 第139回中部日本整形外科災害外科学会・学術集会, 2022年10月脊椎転移手術後全身状態 早期悪化症例の検討 ー術前血液検査結果からみた危険因子ー口頭発表（一般）
- 第30回日本腰痛学会脊椎転移に対する集学的治療は予後を延長させる口頭発表（一般）
- 第84回神戸整形外科セミナー, 2022年10月難治性疼痛を有する脊椎疾患の治療戦略～トラマドール製剤を中心に～[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- The 3rd BioSpine Japan, 2022年10月Development of treatment for intervertebral disc degeneration by selective interference of the mTOR signaling pathway using the CRISPR–Cas9 system口頭発表（一般）
- 第37回日本整形外科学会基礎学術総会, 2022年10月体幹コルセット採型における石膏包帯使用時と3Dデジタルスキャナ使用時の精度の比較口頭発表（一般）
- 第37回日本整形外科学会基礎学術総会, 2022年10月椎間板におけるTRPV4のオートファジーと細胞外マトリクス合成への関与口頭発表（一般）
- 第37回日本整形外科学会基礎学術総会, 2022年10月アディポネクチン受容体アゴニストAdipoRonの椎間板細胞へ与える影響に関する研究ポスター発表
- 第37回日本整形外科学会基礎学術総会, 2022年10月椎間板恒常性維持を目指した変性予防・組織修復の試み[招待有り]シンポジウム・ワークショップパネル（指名）
- ジクトルテープ75mg効能追加記念web講演会in神戸, 2022年09月腰痛症や頚肩腕症候群に対する治療戦略～ジクロフェナクナトリウム経皮吸収型持続性疼痛治療剤への期待～[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第54回脊椎同好会, 2022年09月頸椎症性脊髄症術後1ヶ月で硬膜外血腫が生じた１例口頭発表（一般）
- 第29回日本脊椎・脊髄神経手術手技学会, 2022年09月当院における脊椎転移術後創離開のリスク因子の検討と予防のための新たな試み口頭発表（一般）
- The 10th Japan Association of Spine surgeons with Ambition, 2022年08月脊椎転移手術における術後合併症リスク因子の検討口頭発表（一般）
- 灘区医師会生涯教育Web講演会, 2022年07月脊椎疾患で生じる中枢性・末梢性神経障害性疼痛の診断と治療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 神戸 Pain Relief, 2022年07月脊椎疾患で生じる難治性疼痛の治療戦略～オピオイド誘発性便秘症対策も含めて～[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第4回脊椎腫瘍・骨粗鬆症研究会, 2022年07月TESを施行できなかった胸椎動脈瘤様骨嚢腫の1例口頭発表（一般）
- The 12nd Annual Meeting, Cervical Spine Research Society Asia Pacific Section, 2022年06月Outcomes and risk factors for cervical spine metastasis surgery: a prospective study of 46 cases口頭発表（一般）
- 加西市医師会学術講演会, 2022年06月脊椎疾患の診療で経験する神経障害性疼痛の診断と治療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 北神整形外科Webセミナー, 2022年05月脊椎疾患の診療で遭遇する神経障害性疼痛の診断と治療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第95回日本整形外科学会学術総会, 2022年05月「ロコモ」患者における「ロコトレ」体操の脊柱アライメント・立位バランス改善効果ポスター発表
- 第95回日本整形外科学会学術総会, 2022年05月椎間板再生の基礎と臨床（未来）[招待有り]シンポジウム・ワークショップパネル（指名）
- Seminar for Safe Cervical Spine Surgery 2022, 2022年05月重度頚椎後弯症例の1例[招待有り]口頭発表（一般）
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月The efficacy of growth differentiation factor-6 on the three-dimensionally cultured human intervertebral disc cells and rat tail puncture modelポスター発表
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月Protective roles of Atg5-dependent autophagy against human and rat disc cellular apoptosis and senescence: an in-vitro and in-vivo loss-of-function study口頭発表（一般）
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月A retrospective study about the outcome of spinal metastasis surgery for the patients aged 80 years or older compared to those aged younger than 70 yearsポスター発表
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月Transient Receptor Potential Vanilloid 4 (TRPV4) knockdown suppresses autophagy in rat intervertebral disc cellsポスター発表
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月Improved sagittal spinal alignment and standing body balance by a “locomotion training” rehabilitation program in patients with “locomotive syndrome”口頭発表（一般）
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月Polyethylene tapes at the proximal end of fusion reduce the revision rate related with Proximal Junctional Kyphosis in long spinal fusionsポスター発表
- The 48th Annual Meeting, International Society for the Study of the Lumbar Spine, 2022年05月Prospective study for risk factors of postoperative complication of surgery for spinal metastasisポスター発表
- The 48th Annual Meeting, International Society for the Study of the Lumbar SpineEffect of Adiponectin receptor agonist AdipoRon on human intervertebral disc cell in a three-dimensional cell culture and rat tail puncture modelポスター発表
- The 48th Annual Meeting, International Society for the Study of the Lumbar SpineSurgical outcome of scoliosis with muscular dystrophyポスター発表
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月内視鏡下腰椎椎間板ヘルニア摘出術(MED)における術後再発危険因子の検討口頭発表（一般）
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月脊椎転移手術における術後合併症リスク因子の検討口頭発表（一般）
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月「ロコモ」患者への「ロコトレ」体操の脊柱アライメント・立位バランス改善効果口頭発表（一般）
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月ラット尾部穿刺モデルを用いたGrowth Differentiation Factor-6の椎間板細胞に与える影響に関する研究口頭発表（一般）
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月体幹コルセット採型における石膏包帯使用時と3Dデジタルスキャナを使用時の比較検討口頭発表（一般）
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月80歳以上の超高齢脊椎転移患者に対する手術成績の検討－70歳未満の脊椎転移患者と比較して－ポスター発表
- 第51回日本脊椎脊髄病学会学術集会, 2022年04月アディポネクチン受容体アゴニストAdipoRonの椎間板細胞へ与える影響に関する研究ポスター発表
- 第51回日本脊椎脊髄病学会学術集会GCIB照射がPEEK製椎弓根スクリューの引き抜き強度に与える影響口頭発表（招待・特別）
- 第457回整形外科集談会京阪神地方会, 2022年02月頚胸椎後縦靭帯骨化症術後に生じた滲出液産生腫瘤の1例口頭発表（一般）
- 第57回脊椎外科を学ぶ会, 2022年02月馬尾生検により確定診断に至った原発性馬尾神経悪性リンパ腫の一例口頭発表（一般）
- The68th Annual Meeting, Orthopaedic Research SocietyEffect of Adiponectin receptor agonist AdipoRon on human intervertebral disc cell in a three-dimensional cell culture and rat tail puncture modelポスター発表
- The 68th Annual Meeting, Orthopaedic Research SocietyThe efficacy of growth differentiation factor-6 on the three-dimensionally cultured human intervertebral disc cells and rat tail puncture modelポスター発表
- 第2回 BioSpine Japan, 2022年01月Involvement of Atg5-dependent autophagy in the homeostasis maintenance of rat intervertebral discs: an in-vitro and in-vivo study口頭発表（一般）
- 整形外科連携WEBセミナー, 2021年10月脊椎変性疾患に関連した神経障害性疼痛の診断と治療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第6回兵庫ロコモと骨粗鬆症を語る会, 2021年10月「ロコモティブシンドローム（ロコモ）」に対する「ロコモーショントレーニング（ロコトレ）」の脊柱アライメント・立位バランス改善効果[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第56回脊椎外科を学ぶ会, 2021年10月頚胸椎後縦靭帯骨化症後方術後に生じた滲出液産生腫瘤の1例 –コロコロの正体-口頭発表（一般）
- 第36回日本整形外科学会基礎学術総会, 2021年10月細胞低接着性コラーゲン（Low Adhesive Scaffold Collagen: LASCol）を用いた脊椎椎間板組織修復の試み[招待有り]シンポジウム・ワークショップパネル（指名）
- 第36回日本整形外科学会基礎学術総会, 2021年10月三次元細胞培養を用いたアディポネクチン受容体アゴニストAdipoRon投与に対するヒト椎間板細胞へ与える影響の検討口頭発表（一般）
- 第15回兵庫県骨転移治療研究会, 2021年10月当院における脊椎転移術後創離開のリスク因子の検討と予防のための新たな試み口頭発表（一般）
- 第30回日本脊椎インストゥルメンテーション学会GCIB照射がPEEK製椎弓根スクリューの引き抜き強度に与える影響口頭発表（招待・特別）
- 第53回脊椎外科同好会, 2021年09月診断に難渋した硬膜内髄外腫瘍の1例口頭発表（一般）
- Orthopaedics Web Seminar, 2021年09月整形外科・脊椎外科に関連した神経障害性疼痛の診断と治療－特に保存治療例と術発症例について－[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第2回脊椎腫瘍・骨粗鬆症研究会, 2021年06月Separation surgery後にIMRTを 行った胸椎原発骨肉腫の1例口頭発表（一般）
- 北神戸整形外科Webセミナー, 2021年06月脊椎疾患関連の神経障害性疼痛の診断と治療[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineTrends and measures against postoperative wound dehiscence after surgery for spinal metastasis.ポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineA retrospective analysis of patients with early deterioration of general condition after spinal metastasis surgery: Could we predict the early deterioration with the preoperative blood test?ポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineImproved sagittal spinal alignment and balance by a “locomotion training” rehabilitation program in patients with “locomotive syndrome.ポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineInvolvement of autophagy in human lumbar spine herniated and degenerative disc diseases.ポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineMaintenance of rat intervertebral disc homeostasis via Atg5-dependent autophagy in vitro and in vivoポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineEffect of Adiponectin receptor agonist AdipoRon on human intervertebral disc cell in a three-dimensional cell cultureポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpineEfficacy of growth differentiation factor-6 on three-dimensionally cultured human intervertebral disc cells and a rat tail puncture modelポスター発表
- The47th Annual Meeting, International Society for the Study of the Lumbar SpinePolyethylene tapes at the proximal end in long spinal fusions reduce the revision rate due to Proximal Junctional Kyphosisポスター発表
- 第94回日本整形外科学会学術総会広範囲矯正固定手術における固定近位端のポリエチレンテープの使用はproximal junctional kyphosisに伴う再手術率を低下させるポスター発表
- 第94回日本整形外科学会学術総会「ロコモ」患者へ「ロコトレ」体操が及ぼす脊柱アライメントと立位バランスの改善効果ポスター発表
- 第94回日本整形外科学会学術総会術前血液検査結果から見た脊椎転移手術後全身状態早期悪化の危険因子の検討口頭発表（一般）
- 第94回日本整形外科学会学術総会脊椎転移に対する集学的治療の効果と限界[招待有り]シンポジウム・ワークショップパネル（指名）
- 第94回日本整形外科学会学術総会費用対効果から見た脊椎転移に対する手術加療の効果と課題[招待有り]シンポジウム・ワークショップパネル（指名）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月広範囲矯正固定手術における固定近位端のポリエチレンテープの使用はProximal Junctional Kyphosis及びそれに伴う再手術率を低下させるポスター発表
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月「ロコモ」患者に対する「ロコトレ」体操の脊柱アラインメント・立位バランス改善効果口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月腰椎椎間板変性検体とヘルニア検体におけるオートファジー活性は疾患よりも年齢と変性度に依存する口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月三次元培養したヒト椎間板細胞とラット尾部穿刺モデルにおける成長因子Growth differentiation factor 6投与の有効性口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月三次元細胞培養を用いたアディポネクチン受容体アゴニストAdipoRon投与に対するヒト椎間板細胞へ与える影響の検討口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月ラット椎間板の恒常性維持に関するAtg5依存症オートファジーの役割口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月脊椎転移手術の術後創離開に関する対策口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月分離すべり症に対する椎間孔拡大を主目的とするMIS-TLIFの手術成績 —分離部除圧は必要か？—口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月低侵襲腰椎椎体間固定術（MIS-TLIF）における術後矯正損失を起こす危険因子の検討口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月青年期仙骨疲労骨折の治療経験口頭発表（一般）
- 第50回日本脊椎脊髄病学会学術集会, 2021年04月腰椎分離症に対するCTによる骨癒合評価と被爆量から考える問題点口頭発表（一般）
- 第136回中部日本整形外科災害外科学会学術集会, 2021年04月, 日本語広範囲矯正固定手術において固定近位端でのポリエチレンテープの使用はPJKに伴う再手術率を低下させるシンポジウム・ワークショップパネル（公募）
- 第136回中部日本整形外科災害外科学会学術集会, 2021年04月, 日本語ラット椎間板恒常性維持に対するAtg5依存性オートファジーの関与：ラット細胞・動物実験の検討口頭発表（一般）
- 痛みの治療フォーラム ～Web Seminar～, 2021年02月, 日本語脊椎疾患由来の神経障害性疼痛の診断と治療[招待有り]口頭発表（招待・特別）
- 第20回Takasago Orthopaedic Clinical Conference（高砂整形外科医会）, 2021年02月, 日本語脊椎疾患から生じる神経障害性疼痛の診断と治療[招待有り]口頭発表（招待・特別）
- The 67th Annual Meeting, Orthopaedic Research Society, 2021年02月, 英語Involvement of Atg5-dependent autophagy in maintaining rat intervertebral disc homeostasis口頭発表（一般）
- The 67th Annual Meeting, Orthopaedic Research Society, 2021年02月, 英語Effect of Adiponectin receptor agonist AdipoRon on human intervertebral disc cell in a three-dimensional cell cultureポスター発表
- The 67th Annual Meeting, Orthopaedic Research Society, 2021年02月, 英語The efficacy of growth differentiation factor-6 on the three-dimensionally cultured human intervertebral disc cells and rat tail puncture modelポスター発表
- 第55回脊椎外科を学ぶ会, 2021年02月, 日本語軟骨肉腫に対して肋骨椎体合併切除術を施行した1例口頭発表（一般）
- 第22回圧迫性脊髄症研究会, 2021年01月Separation surgery後に強度変調放射線治療(IMRT)を行った脊椎腫瘍の2例口頭発表（一般）
- 第10回DDS再生医療研究会, 2020年12月, 日本語がん骨転移局所制御に対する徐放化抗がん剤の有効性と安全性についての検討口頭発表（一般）
- The 4th Annual Meeting, Korean Biospine Society, 2020年12月, 英語Roles of Atg5-dependent autophagy in rat intervertebral disc homeostasis: an implication of gene therapy approach口頭発表（一般）
- 第1回脊椎腫瘍・骨粗鬆症研究会, 2020年12月, 日本語軟骨肉腫に対して肋骨部分椎体合併切除術を施行した1例口頭発表（一般）
- 第28回日本腰痛学会, 2020年10月, 日本語腰椎分離症において腰痛発症からの罹患期間が病期に及ぼす影響口頭発表（一般）
- 第28回日本腰痛学会, 2020年10月, 日本語青年期仙骨疲労骨折の治療経験口頭発表（一般）
- 第6回神戸整形外科Clinical skill-up course, 2020年11月, 日本語講師[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第54回日本側彎症学会学術集会, 2020年11月, 日本語小児脊柱変形初回矯正手術後の手術部位感染：多施設研究における病態と危険因子の解析口頭発表（一般）
- 第54回日本側彎症学会学術集会, 2020年11月, 日本語小児側弯症患者におけるインストゥルメント関連合併症の発生率とその特徴口頭発表（一般）
- 第54回日本側彎症学会学術集会, 2020年11月, 日本語小児脊柱変形に対する初回固定術後の予定外手術の頻度およびリスク因子に関する多施設研究口頭発表（一般）
- 第54回日本側彎症学会学術集会, 2020年11月, 日本語小児脊柱変形手術における神経合併症発生調査とリスク因子口頭発表（一般）
- 第35回日本整形外科学会基礎学術集会, 2020年10月, 日本語GCIB照射がPEEK製椎弓根スクリューの引き抜き強度に与える影響口頭発表（一般）
- 第35回日本整形外科学会基礎学術集会, 2020年10月, 日本語三次元培地を用いた成長因子growth differentiation factor-6投与がヒト椎間板細胞に与える影響の検討口頭発表（一般）
- 第35回日本整形外科学会基礎学術集会, 2020年10月, 日本語ラット椎間板の恒常性維持におけるAtg5依存性オートファジーの関与口頭発表（一般）
- 第20回日本Men’s Health医学会・シンポジウム1～疼痛・緩和ケアを考える～, 2020年10月, 日本語脊椎疾患による神経障害性疼痛の診断と治療[招待有り]シンポジウム・ワークショップパネル（指名）
- 第135回中部日本整形外科災害外科学会学術集会, 2020年10月, 日本語脊椎転移手術の術後創離開に関する傾向と対策シンポジウム・ワークショップパネル（公募）
- 第53回日本整形外科学会骨軟部腫瘍学術集会, 2020年09月, 日本語脊椎腫瘍に対するseparation surgeryとIMRTの併用による治療成績－7例のケースシリーズ－ポスター発表
- 第53回日本整形外科学会骨軟部腫瘍学術集会, 2020年09月, 日本語ゼラチンハイドロゲルを用いた徐放化シスプラチン局所投与による新たなる骨転移治療ポスター発表
- Pain Live Symposium, 2020年09月, 日本語ロコモ対策と脊椎疾患に対する薬物治療[招待有り]口頭発表（招待・特別）
- 第49回日本リウマチの外科学会, 2020年09月, 日本語リウマチ性頚椎不安定性の進行と予後予測因子：10年以上に及ぶ前向き追跡調査結果[招待有り]シンポジウム・ワークショップパネル（指名）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語三次元培地を用いた成長因子Growth differentiation factor 6投与がヒト椎間板細胞に与える影響の検討ポスター発表
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語転移性頚椎腫瘍に対する後方手術成績と術後成績不良因子の検討ポスター発表
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語脊椎転移手術における全身状態早期悪化例の検討－術前血液検査結果に着目して－ポスター発表
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語ラット椎間板の恒常性維持におけるAtg5依存症オートファジーの関与口頭発表（一般）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語徐放化シスプラチン局所投与による新たなる脊椎転移制御の試み－マウス骨転移モデルでの検討－口頭発表（一般）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語Long fusionにおいてポリエチレンテープの使用はProximal Junctional Kyphosis (PJK)に伴う再手術率を低下させる口頭発表（一般）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語仙骨骨折を合併した骨盤輪骨折に対するSacral-Aral-lliac Screwを用いた腰仙椎後側法固定術の中長期成績口頭発表（一般）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語骨減少を伴ったRA重度頚椎病変に対する手術治療の工夫[招待有り]口頭発表（招待・特別）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語リウマチ性頚椎不安定性の進行と予後予測因子：5年以上・10年以上の前向き追跡調査結果[招待有り]口頭発表（招待・特別）
- 第49回日本脊椎脊髄病学会学術集会, 2020年09月, 日本語慢性腰痛症に対する薬物療法の合併症評価（肝腎機能を中心に）：日本脊椎脊髄病学会主導多施設前向き追跡調査シンポジウム・ワークショップパネル（公募）
- 第93回日本整形外科学会学術総会, 2020年06月, 日本語頚椎転移の手術成績と成績不良因子の検討口頭発表（一般）
- 第93回日本整形外科学会学術総会, 2020年06月, 日本語Long fusionにおける固定近位端の固定法の違いによるProximal Junctional Kyphosis(PJK)に伴う再手術率の比較検討ポスター発表
- 第93回日本整形外科学会学術総会, 2020年06月, 日本語筋ジストロフィーに伴う脊柱変形の手術経験ポスター発表
- 第93回日本整形外科学会学術総会, 2020年06月, 日本語「ロコトレ」体操が及ぼす「ロコモ」患者の脊柱アラインメントと体幹バランス改善効果口頭発表（一般）
- 第57回日本リハビリテーション医学会学術集会, 2020年08月, 日本語頸椎転移患者の手術成績と成績不良因子の検討－PS、QOLの推移から－口頭発表（一般）
- 第73回神戸整形外科セミナー, 2020年07月, 日本語脊椎疾患の神経障害性疼痛に対する治療戦略～ミロガバリンへの期待を含めて～[招待有り]口頭発表（基調）
- 第134回中部日本整形外科災害外科学会学術集会, 2020年04月, 日本語頸椎転移に対する後方手術成績と術後成績不良因子の検討口頭発表（一般）
- 兵庫Pain Conference, 2020年02月, 日本語ロコモティブシンドロームへの運動・薬物治療－脊椎疾患を中心に－[招待有り]口頭発表（招待・特別）
- Pain Live Symposium in Kobe, 2020年02月, 日本語脊椎疾患で生じる神経障害性疼痛の診断と治療[招待有り]口頭発表（招待・特別）
- 第5回AKASHI Pharmacy Director Seminar, 2020年02月, 日本語脊椎疾患に由来する神経障害性疼痛の診断と治療[招待有り]口頭発表（招待・特別）
- 第12回兵庫県転移性骨腫瘍治療研究会, 2020年02月, 日本語脊椎転移手術における早期成績不良例に関する検討口頭発表（一般）
- The 66th Annual Meeting, Orthopaedic Research Society, 2020年02月, 英語Involvement of Atg5-dependent autophagy in the maintenance of rat intervertebral disc homeostasis in vitro and in vivoポスター発表
- The 66th Annual Meeting, Orthopaedic Research Society, 2020年02月, 英語The local administration of gelatin hydrogel microspheres incorporating cisplatin enhanced anti-tumor effects with less side effects in vivo bone metastasis modelポスター発表
- The 66th Annual Meeting, Orthopaedic Research Society, 2020年02月, 英語Involvement of autophagy in human herniated and degenerative intervertebral disc diseasesポスター発表
- 神戸市医師会学術講演会, 2019年12月, 日本語ロコモティブシンドロームへの運動・薬物治療－脊椎疾患を中心に－[招待有り]口頭発表（基調）
- 第9回DDS再生医療研究会, 2019年12月, 日本語ゼラチンハイドロゲルを用いた徐放化シスプラチン局所投与によるがん骨転移局所制御口頭発表（一般）
- 明石医師会内科医会学術講演会, 2019年11月, 日本語脊椎疾患に関連した神経障害性疼痛の診断と治療[招待有り]口頭発表（招待・特別）
- 神戸市整形外科カンファレンス, 2019年11月, 日本語ロコモティブシンドロームの診断・評価・治療－脊椎疾患を中心に－[招待有り]口頭発表（基調）
- The 47th Annual Meeting, Cervical Spine Research Society, 2019年11月, 英語Surgical outcome of cervical spine metastasis: a prospective study of 45 casesポスター発表
- The 47th Annual Meeting, Cervical Spine Research Society, 2019年11月, 英語Involvement of autophagy in human cervical spine degenerated and herniated discs口頭発表（一般）
- 塩野義製薬社内講演会, 2019年10月, 日本語ロコモティブシンドロームへの運動・薬物治療介入－脊椎疾患を中心に－[招待有り]口頭発表（招待・特別）
- The 1st Meeting, BioSpine Japan, 2019年10月, 英語A novel new method for bone metastasis using gelatin hydrogel incorporating anti-tumor drug as a sustained release system口頭発表（一般）
- 第34回日本整形外科学会基礎学術集会, 2019年10月, 日本語徐放化抗がん剤局所投与による新たなる骨転移制御の試み口頭発表（一般）
- 第34回日本整形外科学会基礎学術集会, 2019年10月, 日本語ラット脊椎椎間板の恒常性維持におけるAtg5依存性オートファジーの関与口頭発表（一般）
- 第34回日本整形外科学会基礎学術集会, 2019年10月, 日本語腰椎椎間板におけるオートファジー活性は疾患よりも年齢と変性度に依存する口頭発表（一般）
- 第34回日本整形外科学会基礎学術集会, 2019年10月, 日本語オートファジーの制御による椎間板変性治療の可能性[招待有り]シンポジウム・ワークショップパネル（指名）
- 兵庫県薬剤師会東播支部・兵庫県病院薬剤師会共催研修会, 2019年09月, 日本語ロコモティブシンドロームに対する運動・薬物療法－脊椎疾患を中心に－[招待有り]口頭発表（招待・特別）
- 高齢者医療病診連携の会, 2019年09月, 日本語ロコモティブシンドロームに対する運動・薬物療法－脊椎疾患を中心に－[招待有り]口頭発表（招待・特別）
- 第133回中部日本整形外科災害外科学会学術集会, 2019年09月, 日本語治療に難渋したアテトーゼ型脳性麻痺性頚髄症の1例口頭発表（一般）
- 第27回日本腰痛学会, 2019年09月, 日本語ラット脊椎椎間板の恒常性維持におけるAtg5依存性オートファジーの関与口頭発表（一般）
- 第26回日本脊椎・脊髄神経手術手技学会学術集会, 2019年09月, 日本語脊椎転移に対する手術療法の効果[招待有り]シンポジウム・ワークショップパネル（指名）
- 第8回Japan Association of Spine Surgeons with Ambition, 2019年08月, 日本語脊椎転移手術における早期成績不良例に関する検討口頭発表（一般）
- 第52回脊椎外科同好会, 2019年08月, 日本語重度頚椎後弯に対して一期的前後方手術を施行した1例～knack&pitfalls～口頭発表（一般）
- 明石市医師会外科系医会講演会, 2019年07月, 日本語ロコモティブシンドロームに対する運動療法と薬物療法[招待有り]口頭発表（招待・特別）
- 兵庫県薬剤師会摂丹支部・兵庫県病院薬剤師会摂丹支部共催研修会, 2019年06月, 日本語末梢性神経障害性疼痛における薬剤選択、治療について－整形外科・脊髄外科の立場から－[招待有り]口頭発表（招待・特別）
- 第44回日本外科系連合学会学術集会, 2019年06月脊椎転移に対する集学的治療は予後を延長させる[招待有り]シンポジウム・ワークショップパネル（指名）
- 第1回Kansai Cervical Spine研究会, 2019年06月, 日本語頸椎転移の手術成績－前向きコホート研究による45例の検討－口頭発表（一般）
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語Selective mTORC1 inhibition by temsirolimus protects human disc nucleus pulposus cells through Akt and autophagy inductionポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語Involvement of ATG5-dependent autophagy in the maintenance of rat intervertebral disc homeostasis in vitro and in vivoポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語What makes the early outcome of spinal metastasis surgery unsatisfactory? A retrospective studyポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語The factor lowering the cost-utility of surgical treatment for patients with metastatic spinal tumorポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語The role of integrinα5β1 in the alteration of notochordal cell induced by dynamic loadingポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語Effect of spinal surgery on prognosis in patients with symptomatic spinal metastasis: a prospective cohort study口頭発表（一般）
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語Involvement of autophagy in human lumbar spine degenerated and herniated disc diseasesポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語Improvement of the sagittal alignment and balance of the spine through a “locomotion training” rehabilitation program in patients with locomotive syndromeポスター発表
- The 46th Annual Meeting, International Society for the Study of the Lumbar Spine, 2019年06月, 英語Autophagy plays protective roles against human disc cellular apoptosis and senescence, but not affect extracellular matrix degradation口頭発表（一般）
- 第56回日本リハビリテーション医学会学術集会, 2019年06月「ロコトレ」理学療法プログラムによる「ロコモ」患者の脊柱アライメントと体幹バランス改善効果口頭発表（一般）
- 第92回日本整形外科学会学術総会, 2019年05月70歳以上の脊椎転移患者における手術効果とその経時的推移口頭発表（一般）
- 第92回日本整形外科学会学術総会, 2019年05月脊椎転移の症候化リスク因子に関する前向き研究口頭発表（一般）
- 第92回日本整形外科学会学術総会, 2019年05月「ロコトレ」体操による「ロコモ」患者の脊柱アライメントと体幹バランス改善効果口頭発表（一般）
- 第132回中部日本整形外科災害外科学会学術集会, 2019年04月70歳以上の脊椎転移患者における手術成績口頭発表（一般）
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月腰椎変性すべり症に対する前後合併椎体間固定術と後方椎体間固定術の手術成績－多施設比較検討－ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月動的圧迫負荷による脊索由来細胞の変化とintegrinα5β1の果たす役割ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月mTOR阻害薬テムシロリムスはAktとオートファジーの誘導しヒト椎間板髄核細胞に保護作用を来すポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月術後10年以上に経過観察しえた胸腰椎・腰椎部先天性後側弯症・後弯症における16症例の立位矢状面バランスの検討ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月脊椎転移手術における早期成績不良例に関する検討ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月骨転移Cancer Boardの効果と課題ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月筋ジストロフィーに伴う脊柱変形の手術経験ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月脊椎インスツルメント術後創部感染に対する局所閉鎖陰圧療法の有用性と失敗因子の検討ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月成人脊柱変形手術において多椎間TLIFとPonte osteotomyのみで十分な腰椎前弯を獲得できるか？ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月70歳以上の転移性脊椎腫瘍患者における手術成績口頭発表（一般）
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月転移性脊椎腫瘍に対する手術加療の費用対効用を低下させる因子の検討
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月脊椎椎間板におけるオートファジー活性は疾患よりも年齢と変性度に依存する（腰椎椎間板ヘルニア検体と固定術検体との比較）ポスター発表
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月症候性側弯症手術における電磁気センサー付き椎弓根プローブの有用性口頭発表（一般）
- 第48回日本脊椎脊髄病学会学術集会, 2019年04月「ロコトレ」リハビリプログラムによる「ロコモ」患者の脊柱アライメントと体幹バランス改善効果口頭発表（一般）
- 第31回下西集談会, 2019年03月, 日本語, 下京西部医師会, 京都, 国内会議認知機能がロコモ度に及ぼす影響について口頭発表（一般）
- 第9回日本成人脊柱変形学会, 2019年03月, 日本語, 日本成人脊柱変形学会, 東京, 国内会議ロコモ体操に準じた理学療法プログラムの脊柱アライメントと体幹バランス改善効果口頭発表（一般）
- The 10th Annual Meeting of Cervical Spine Research Society Asia Pacific Section, 2019年03月, 英語, Cervical Spine Research Society Asia Pacific Section, 横浜, 国際会議Involvement of autophagy in human cervical spine discs from spondylosis or herniation口頭発表（一般）
- 第10回兵庫県骨転移治療研究会, 2019年02月症候性脊椎転移の発生リスクに関する前向き研究口頭発表（招待・特別）
- 第51回脊椎外科を学ぶ会, 2019年02月, 日本語, 大阪, 国内会議脳性麻痺性頚髄症に対して繰り返し手術を要した1例口頭発表（一般）
- The 65th Annual Meeting of Orthopaedic Research Society, 2019年02月, 英語, Orthopaedic Research Society, Austin, 国際会議The local administration of sustained release of cisplatin by gelatin hydrogel enhanced anti-tumor effect and reduced side effect: the preliminary study using bone metastasis animal modelポスター発表
- The 65th Annual Meeting of Orthopaedic Research Society, 2019年02月, 英語, Orthopaedic Research Society, Austin, 国際会議Regenerative Potential of the Damaged Intervertebral Disc by the Low Adhesive Scaffold Collagen (LASCol)ポスター発表
- The 65th Annual Meeting of Orthopaedic Research Society, 2019年02月, 英語, Orthopaedic Research Society, Austin, 国際会議Involvement of autophagy in human intervertebral disc degeneration and herniationポスター発表
- The 65th Annual Meeting of Orthopaedic Research Society, 2019年02月, 英語, Orthopaedic Research Society, Austin, 国際会議A study of the fate of notochordal cell in the process of the intervertebral disc degeneration using a dynamic loading organ culture systemポスター発表
- The 65th Annual Meeting of Orthopaedic Research Society, 2019年02月, 英語, Orthopaedic Research Society, Austin, 国内会議A Newly Developed Low Adhesive Scaffold Collagen (LASCol) Accelerates Bone Healing in a Rat Femur Osteotomy Modelポスター発表
- 第3回日本抗加齢協会学術フォーラム, 2018年12月, 日本語, 日本抗加齢協会, 大阪, 国内会議ロコモ体操による脊柱アライメント改善効果－手術によらない脊柱変形改善の試み－[招待有り]シンポジウム・ワークショップパネル（指名）
- 第40回日本バイオマテリアル学会大会, 2018年11月椎間板組織再生のための細胞低接着性コラーゲンゲルの開発口頭発表（一般）
- 第2回日本リハビリテーション医学会秋季学術集会, 2018年11月, 日本語, 日本リハビリテーション医学会, 仙台, 国内会議脊椎転移の症候化リスク因子の前向き検討口頭発表（一般）
- 第8回DDS再生医療研究会 / 第10回多血小板血漿(PRP)療法研究会, 2018年11月, 日本語, 多血小板血漿(PRP)療法研究会, 大阪, 国内会議細胞低接着性コラーゲン(LASCol)を用いた脊椎椎間板再生の可能性口頭発表（一般）
- 第52回日本側彎症学会学術集会, 2018年11月, 日本語, 日本側彎症学会, 東京, 国内会議筋ジストロフィーに伴う側弯症の手術成功口頭発表（一般）
- 第2回日本リハビリテーション医学会秋季学術集会, 2018年11月, 日本語, 日本リハビリテーション医学会, 仙台, 国内会議ロコモ体操の脊椎・骨盤・下肢矢状面アライメント改善効果－有効性とその限界－口頭発表（一般）
- 神戸脊椎を考える会, 2018年11月, 日本語, Kobe Spine Conference for Young Clinicians, 神戸, 国内会議ロコモ体操による脊柱アライメントと体幹バランスの改善効果口頭発表（基調）
- 第46回日本関節病学会, 2018年11月, 日本語, 日本関節病学会, 岡山, 国内会議リウマチ性頸椎不安定性の進行と予後予測因子：10年以上の前向き追跡調査結果[招待有り]シンポジウム・ワークショップパネル（指名）
- 第8回DDS再生医療研究会 / 第10回多血小板血漿(PRP)療法研究会, 2018年11月, 日本語, 多血小板血漿(PRP)療法研究会, 大阪, 国内会議ゼラチンハイドロゲルを用いた徐放化抗がん剤局所投与による骨転移局所制御口頭発表（一般）
- 第2回日本リハビリテーション医学会秋季学術集会, 2018年11月, 日本語, 日本リハビリテーション医学会, 仙台, 国内会議70歳以上の脊椎転移患者の手術成績 -PS、ADL、QOLの推移から-口頭発表（一般）
- Depuy Synthes Combined Cadaveric Course in Bangkok, 2018年10月, 日本語講師[招待有り]公開講演，セミナー，チュートリアル，講習，講義等
- 第33回日本整形外科学会基礎学術集会, 2018年10月, 日本語, 日本整形外科学会, 奈良, 国内会議動的圧迫負荷が,integrina5B1を介して脊索由来細胞に与える影響ポスター発表
- 第131回中部日本整形外科災害外科学会学術集会, 2018年10月, 日本語, 中部日本整形外科災害外科学会, 岡山, 国内会議脊椎転移に対する手術は予後を延長させる口頭発表（一般）
- 第33回日本整形外科学会基礎学術集会, 2018年10月, 日本語, 日本整形外科学会, 奈良, 国内会議脊椎椎間板におけるオートファジー活性は疾患よりも年齢と変性度に依存するポスター発表
- 2018 Kobe Rosai Almuni Club, 2018年10月, 日本語, 神戸労災病院, 神戸, 国内会議四肢のしびれ・運動麻痺[招待有り]口頭発表（招待・特別）
- 第33回日本整形外科学会基礎学術集会, 2018年10月, 日本語, 日本整形外科学会, 奈良, 国内会議細胞低接着性コラーゲン（low adhesive scaffold collagen: LASCol）を用いた脊椎椎間板再生の試み口頭発表（一般）
- 第33回日本整形外科学会基礎学術集会, 2018年10月, 日本語, 日本整形外科学会, 奈良, 国内会議がん骨転移モデルに対するゼラチンハイドロゲルを用いた徐放化抗がん剤局所投与の有効性ポスター発表
- 第33回日本整形外科学会基礎学術集会, 2018年10月, 日本語, 日本整形外科学会, 奈良, 国内会議mTOR阻害薬テムシロリムスがヒト椎間板髄核細胞に及ぼす保護作用はAktとオートファジーの誘導に由来する口頭発表（一般）
- 第73回日本体力医学会大会, 2018年09月, 日本語, 日本体力医学会大会, 福井, 国内会議ロコモ度が脊椎アライメントに及ぼす影響口頭発表（一般）
- 5th Tissue Engineering and Regenerative Medicine International Society World Congress, 2018年09月, 英語, Tissue Engineering and Regenerative Medicine International Society, 京都, 国際会議A Novel Production Method of Gelatin Hydrogel Microsphere as a Sustained Release System of Cisplatin Aiming for Clinical Applicationポスター発表
- 第51回脊椎外科同好会, 2018年08月, 日本語, 脊椎外科同好会, 神奈川, 国内会議脳性麻痺性頸椎症性脊髄症、術後偽関節の1例口頭発表（一般）
- 第3回神戸内科塾, 2018年08月, 日本語, 第一三共株式会社, 神戸, 国内会議四肢のしびれ：整形外科の立場から[招待有り]口頭発表（招待・特別）
- The 7th Japan Association of Spine Surgeons with Ambition, 2018年08月, 日本語, Japan Association of Spine Surgeons with Ambition, 広島, 国内会議ロコモ体操の脊椎・骨盤・下肢矢状面アライメント改善効果－有効性とその限界－口頭発表（一般）
- 第51回脊椎外科同好会, 2018年08月, 日本語, 脊椎外科同好会, 神奈川, 国内会議80歳以上の脊椎術後深部感染に対する局所陰圧閉鎖療法の有用性と限界口頭発表（一般）
- NPO法人兵庫脊椎脊髄病医療振興機構 第18回市民公開講座, 2018年07月, 日本語「ロコトレ」を行って「ロコモ」を予防しよう！－いつまでも自分の足で歩き続けるために－[招待有り]口頭発表（招待・特別）
- 第51回日本整形外科骨・軟部腫瘍学術集会, 2018年07月, 日本語, 日本整形外科学会, 静岡, 国内会議不安定性を有する転移性脊椎腫瘍に対する治療 脊椎転移に対する手術療法の効果シンポジウム・ワークショップパネル（公募）
- 第51回日本整形外科骨・軟部腫瘍学術集会, 2018年07月, 日本語, 日本整形外科学会, 静岡, 国内会議脊椎転移に対する手術療法の効果口頭発表（一般）
- 第55回日本リハビリテーション医学会学術集会, 2018年06月, 日本語, 日本リハビリテーション医学会, 福岡, 国内会議新規低接着性コラーゲン(LASCol)はラット大腿骨骨欠損モデルにおいて骨癒合を促進するポスター発表
- 第55回日本リハビリテーション医学会学術集会, 2018年06月, 日本語, 日本リハビリテーション医学会, 福岡, 国内会議細胞低接着性コラーゲン（Low Adhesive Scaffold Collagen: LASCol）による脊椎椎間板再生ポスター発表
- 第91回日本整形外科学会学術総会, 2018年05月, 日本語, 日本整形外科学会, 神戸, 国内会議腰椎変性すべり症に対する前後方間接除圧固定術と後方直接除圧固定術の多施設前向き研究による比較検討－臨床成績の観点からー口頭発表（一般）
- 第91回日本整形外科学会学術総会, 2018年05月, 日本語, 日本整形外科学会, 神戸, 国内会議腰椎変性すべり症に対する前後合併椎体間固定術と後方椎体間固定術の多施設比較検討ー固定椎間のＸ線学的評価ー口頭発表（一般）
- 第91回日本整形外科学会学術総会, 2018年05月, 日本語, 日本整形外科学会, 神戸, 国内会議ロコモティブシンドロームに対するロコモ体操の脊椎・骨盤・下肢矢状断アライメント改善効果口頭発表（一般）
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議The prospective cohort study for the predicting factor of symptomatic spinal metastasisポスター発表
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議The fate of notochordal cell in intervertebral disc degeneration induced by dynamic compressive load through integrin alpha5/beta1 mechanotransductionポスター発表
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議Temsirolimus is a candidate of the optimal mTOR inhibitor to protect human disc cells dependingon Akt and autophagy inductionポスター発表
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議Regenerative Potential of the Intervertebral Disc by Using the Low Adhesive Scaffold Collagen (LASCol)口頭発表（一般）
- 45th International Society for the Study of the Lumbar Spine Annual Meeting, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議Regenerative potential of the intervertebral disc by using the Low Adhesive Scaffold Collagen (LASCol)ポスター発表
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議Protective effects of “locomotion training” exercise against the sagittal malalignment of the spine-pelvis-lower extremity axis in patients with the locomotive syndromeポスター発表
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議Features and problems of corrective long spinal fusion for adult spinal deformity with multiple vertebral fractures due to severe osteoporosisポスター発表
- 34th Annual Meeting Cervical Spine Research Society - Europe, 2018年05月, 英語, Cervical Spine Research Society – European Section (CSRS-ES), Lisbon, 国際会議Complications of posterior fusion for atlantoaxial instability in children with Down syndromeポスター発表
- The 45th International Society for the Study of the Lumbar Spine, 2018年05月, 英語, International Society for the Study of the Lumbar Spine, Banff, 国際会議Autophagy plays protective roles against human disc cellular apoptosis,senescence, and extracellular matrix degradation口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議椎間板動的圧迫負荷が脊索由来髄核細胞に及ぼした影響口頭発表（一般）
- 第130回中部日本整形外科災害外科学会学術集会, 2018年04月, 日本語, 中部日本整形外科災害外科学会, 松山, 国内会議前向きコホート研究による症候性脊椎転移の発生リスクに関する検討口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議仙骨骨折を合併した骨盤輪骨折に対するSacral-Aal-lliac Screw を用いた腰仙椎後側法固定術の有用性口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会学術集会, 神戸, 国内会議脊椎転移に対する集学的治療は予後を延長させる口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議脊椎転移に対する手術加療の費用対効用口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議細胞低接着性コラーゲン（Low Adhesive Scaffold Collagen: LASCol）による脊椎椎間板再生の可能性口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議骨粗鬆に伴う多発椎体骨折を合併した成人脊柱変形手術の特徴と問題点ポスター発表
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議腰椎変性すべり症に対するOblique Lateral Inter-bodyFusion(OLIF)を用いた低侵襲前後合併椎体間固定術と後方椎体間固定術の多施設比較検討口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議ロコモティブシンドロームに関連した脊椎・骨盤・下肢矢状面アライメント障害に対するロコモ体操の改善効果ポスター発表
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議リウマチ頚椎不安定性発生防止のための予測因子― 10年以上の前向き多施設共同研究からの検討 ―口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議オートファジーの抑制はヒト椎間板細胞においてアポトーシス・セネッセンスを誘導するが、細胞外基質代謝への影響は少ない口頭発表（一般）
- 第47回日本脊椎脊髄病学会学術集会, 2018年04月, 日本語, 日本脊椎脊髄病学会, 神戸, 国内会議mTORC1阻害薬テムシロリムスのヒト椎間板髄核細胞保護効果はオートファジー及びAktの活性化に由来する口頭発表（一般）
- 第130回中部日本整形外科災害外科学会学術集会, 2018年04月, 日本語, 中部日本整形外科災害外科学会, 松山, 国内会議Augumented Realityと生体模型により摘出しえた腰部伏針の１例口頭発表（一般）
- 第49回脊椎外科を学ぶ会, 2018年02月, 日本語, 脊椎外科を学ぶ会, 大阪, 国内会議巨大頚胸椎MFHに対してseparation surgeryとIMRTが奏功した1例口頭発表（一般）
- 第32回日本整形外科学会基礎学術集会, 2017年10月, 日本語, 日本整形外科学会, 沖縄, 国内会議ｍTORC1阻害薬テムシロリスムはヒト椎間板髄核細胞において細胞死、細胞老化、細胞外基質分解を抑制するシンポジウム・ワークショップパネル（公募）
- 第32回日本整形外科学会基礎学術集会, 2017年10月, 日本語, 日本整形外科学会, 沖縄, 国内会議脊椎椎間板変性へのオートファジーの関与とその脊索由来細胞における恒常性維持機構の可能性シンポジウム・ワークショップパネル（公募）
- 第129回中部日本整形外科災害外科学会学術集会, 2017年10月, 日本語, 中部日本整形外科災害外科学会, 富山, 国内会議ロコモティブシンドロームに対するロコモ体操の脊椎骨盤矢状面アライメントへの影響口頭発表（一般）
- 第32回日本整形外科学会基礎学術集会, 2017年10月, 日本語, 日本整形外科学会, 沖縄, 国内会議オートファジーの抑制はヒト椎間板細胞においてアポトーシス、セネッセンスを誘導し、細胞数を減少させるシンポジウム・ワークショップパネル（公募）
- 第48回脊椎外科を学ぶ会, 2017年09月, 日本語, 脊椎外科を学ぶ会, 大阪, 国内会議後頭頚（胸）椎固定術後に隣接椎間障害を繰り返し、最終的に仙椎までの固定を要した1例口頭発表（一般）
- 第36回運動器移植再生医学研究会, 2017年09月, 日本語, 運動器移植再生医学研究会, 京都, 国内会議mTORC1阻害薬テムシロリムスはヒト椎間板髄核細胞において細胞死、細胞老化、細胞外基質分解を抑制する口頭発表（一般）
- 第50回脊椎外科同好会, 2017年08月, 日本語, 脊椎外科同好会, 岡山, 国内会議隣接椎間障害を繰り返し最終的に後頭・全脊椎固定術を要した症例口頭発表（一般）
- The 6th Japan Association of Spine Surgeons with Ambition, 2017年08月, 日本語, 千葉大学, 東京, 国内会議症候性脊椎転移の発生リスクに関する前向き研究口頭発表（一般）
- 第50回 日本整形外科学会 骨・軟部腫瘍学術集会, 2017年07月, 日本語, 日本整形外科学会, 東京, 国内会議症候性脊椎転移の発生リスクに関する前向き研究口頭発表（一般）
- 第1回これからの関節リウマチ治療を考える会, 2017年07月, 日本語, これからの関節リウマチ治療を考える会, 神戸, 国内会議リウマチ性頚椎不安定性の進行とその予後予測因子[招待有り]口頭発表（招待・特別）
- 第90回日本整形外科学会学術総会, 2017年05月, 日本語, 日本整形外科学会, 仙台, 国内会議有症状脊椎転移の発生リスクに関する前向き研究ポスター発表
- 第90回日本整形外科学会学術総会, 2017年05月, 日本語, 日本整形外科学会, 仙台, 国内会議最重症型骨粗鬆症性多発脊椎椎体骨折に対する後方矯正固定術の臨床成績-2年以上経過症例を対象として-ポスター発表
- 第90回日本整形外科学会学術総会, 2017年05月, 日本語, 日本整形外科学会, 仙台, 国内会議腰椎変性すべり症に対する前後方間接除圧固定術と後方直接除圧固定術の多施設前向き研究による比較検討ポスター発表
- 第90回日本整形外科学会学術総会, 2017年05月, 日本語, 日本整形外科学会, 仙台, 国内会議がん患者の脊椎転移に対する直視下手術と経皮的後方固定術が及ぼす全身状態、ADL、QOL改善効果の比較ポスター発表
- エーザイ社内講演会, 2017年04月, 日本語腰痛への薬物療法[招待有り]口頭発表（招待・特別）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議椎間板髄核におけるオートファジーの重要性とその脊索表現型保持への関与の可能性口頭発表（一般）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議神経筋原性側弯症に対する脊椎矯正固定術の治療成績と合併症ポスター発表
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議症候性脊椎転移の発生リスクに関する前向き研究口頭発表（一般）
- 第128回中部日本整形外科災害外科学会学術集会, 2017年04月, 日本語, 中部日本整形外科災害外科学会, 神戸, 国内会議症候性脊椎転移の発生リスクに関する前向き研究口頭発表（一般）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議腰椎すべり症に対するOLIFを用いた前後方間接除圧固定術の手術成績―多施設前向き研究による後方直接除圧固定術との比較検討口頭発表（一般）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議近位端の2椎弓ポリエチレンテープ固定の追加はlong fusionにおけるPJKを予防できるか?ポスター発表
- 第3回志国脊椎医龍会, 2017年04月, 日本語, 志国脊椎医龍会, 札幌, 国内会議リウマチ性頚椎不安定性の進行と予後予測因子[招待有り]口頭発表（招待・特別）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議ヒト椎間板髄核臍傍におけるmTOR阻害薬の細胞死、細胞老化、細胞外基質分解抑止効果の比較ポスター発表
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議ハイリスク側弯症症例に対する後方側弯症手術の治療成績と周術期合併症口頭発表（一般）
- 第128回中部日本整形外科災害外科学会学術集会, 2017年04月, 日本語, 中部日本整形外科災害外科学会, 神戸, 国内会議がん患者の脊椎転移に対する直視下手術と経皮的後方固定術の全身状態、ADL、QOL改善効果口頭発表（一般）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議がん患者の脊椎転移に対して直視下手術と経皮的後方固定術が全身状態，ADL，QOLに及ぼす影響の比較ポスター発表
- 第128回中部日本整形外科災害外科学会学術集会, 2017年04月, 日本語, 中部日本整形外科災害外科学会, 神戸, 国内会議Separation surgery後にIMRTを施行した脊椎腫瘍の2例口頭発表（一般）
- 第46回日本脊椎脊髄病学会学術集会, 2017年04月, 日本語, 日本脊椎脊髄病学会, 札幌, 国内会議ATG5のノックダウンによるオートファジーの抑制はヒト椎間板細胞のアポトーシスとセネッセンスを誘導し、細胞数を減少させるポスター発表
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2021年04月01日 - 2024年03月31日mTORC1制御による椎間板変性遺伝子・薬物治療法の開発我々の過去の細胞実験からmTORは細胞に必須のシグナル伝達経路である一方、mTOR複合体1（mTORC1）の選択的な抑制が椎間板変性抑止作用を示す可能性が示唆された。そのため本研究ではラット椎間板変性モデルに対してmTORC1のみを抑制する遺伝子・薬物治療を行い、椎間板変性抑止効果の有無について検討を行った。 まずはmTORC1の選択的な抑制の確立を目指し、ラット椎間板細胞においてmTORC1の構成体であるRaptorへRNA干渉を行う予備実験を試みたところ、Raptorのタンパク発現は50.1%-60.3%のノックダウンを示した。そこでより高精度で特定遺伝子の完全な排除が可能となるCRISPR-Cas9システムの導入を計画し、ヒト脊椎手術で採取した椎間板細胞に発現するRAPTORを標的としてCRISPR-Cas9システムを用いたところ、安定して80%以上のRAPTORタンパク質の発現抑制が得られた。CRISPR-Cas9システムによってRAPTORのタンパク発現がノックアウトされた細胞では顕著なオートファジーの亢進が認められ、mTORシグナル経路の選択的な抑制の達成が確認できた。現在、CRISPR-Cas9システムによるmTORC1の選択的な抑制がアポトーシス細胞死やセネッセンス細胞老化へ及ぼす影響について検討中である。 並行してラット椎間板細胞に対するmTORC1阻害剤テムシロリムスを用いた予備実験を行い、mTORシグナル経路の有効な阻害が確認できた。ラット椎間板変性モデルの作成・確立も進んでおり、現在、Raptorを標的としたRNA干渉のためのsiRNAならびにテムシロリムスの椎間板内局所投与を行う動物実験を実施中である。 以上の結果を受け、①薬剤、②RNA干渉、③CRIPSR-Cas9を用いた椎間板細胞・動物実験をさらに進めていく予定である。
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日アディポネクチンによる椎間板変性・炎症に対する治療法の開発椎間板変性は腰痛の主な原因の一つである.脂肪細胞から分泌されるアディポサイトカインの一つであるアディポネクチンは抗炎症作用を有すると報告されている.アディポネクチンの臨床応用を目指し、アディポネクチン受容体アゴニストであるアディポロン投与が椎間板変性に与える影響を検討した. in vitro実験として腰椎手術時に採取された18例からのヒト椎間板細胞を三次元培地に培養した後に4グループ(Control群: C群, アディポロン投与群: A群, IL-1β投与群: I群, アディポロン+IL-1β投与群: A+I群)に分け, 細胞外基質代謝や炎症性サイトカインへの影響をRT-PCR,蛍光免疫染色,Western Blotting法を用いて検討した. RT-PCRではA+I群ではI群と比較して細胞外基質異化因子MMP-13, ADAMTS-4や炎症性サイトカインTNF-α, IL-6の発現が有意に抑制された(p<0.005). 蛍光免疫染色ではA+I群ではI群と比較してTNF-α, ADAMTS-4の発現が有意に抑制された(p<0.05). Western Blotting法でもA+I群ではI群と比較してMMP-13, ADAMTS-4, TNF-α, IL-6の発現が有意に抑制された(p<0.03). in vivo実験としてラット尾椎針穿刺椎間板変性モデルを用いて3グループ（Control群: C群, 穿刺のみ群: P群, 穿刺後にアディポロン投与群: P+A群）に分け, 経時的に椎間板高を単純X線検査で比較した. P+A群はP群に比べ穿刺後14日及び28日目の時点で椎間板高の減少が有意に抑制された(p=0.001). 以上よりアディポロンは細胞外基質異化因子や炎症性サイトカインの発現低下を通して椎間板変性進行の防止や予防に有用な可能性が示唆された.
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2020年04月01日 - 2023年03月31日徐放化抗がん剤と非金属脊椎インプラントを併用した新しい脊椎転移治療に関する研究現在、ラットを用いた徐放化抗癌剤の効果確認の実験を行っている。 骨転移モデルラットに対して、徐放化抗癌剤を局所投与し、経時的に評価している。 実験系は全てを終えた訳ではないが、投与初期段階での効果は強くなく、有意差を持つには至っていない。今後、N数を増やすなど実験を進める予定である。
非金属脊椎インプラントの研究開発においては、現在、有限要素法においてインプラントの強度試験を実施中である。結果は今後纏める予定である。また、PEEK screwの放射線のartifactに関する実験は、予備実験を行っている段階である。 - 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2019年04月01日 - 2022年03月31日mTORC1を標的とした変形性関節症治療薬の開発正常ヒト軟骨細胞としてNHAC-Kn（Normal Human Articular Chondrocyte-Knee,Lonza社）を購。細胞毒性を評価するために96穴プレートに細胞を播種し、希釈倍率振り分けて薬剤投与し、生細胞率を調べた。まず、ラパマイシン、テムシロリムスを濃度0 , 0.01 , 0.1 , 1 , 10 , 50 μM /mlで(6条件)で振り分け、培養し、各薬剤ともに8時間または24時間培養。培養後、各wellにCCK-8を添加して、2時間培養後に呈色反応を確認した。細胞毒性を450nm 吸光度で測定し、ラパマイシン、テムシロリムス共に0.1μM/mlが至適濃度の可能性が示唆された。また、現在、ヒト軟骨細胞にIL1-betaを投与し、ラパマイシン、テムシロリムスの遺伝子発現変化に対する影響についてReal-time PCRについて調べる実験を行っている。
- 国立研究開発法人日本医療研究開発機構（AMED）, 産学連携医療イノベーション創出プログラム セットアップスキーム（ACT-MS）, 近畿大学・神戸大学・大阪府立大学・神戸医療産業都市推進機構, 2020年08月 - 2022年03月, 研究分担者ヘルニア・変性椎間板組織再生を促す新規コラーゲンゲル充填剤
- 日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2018年04月01日 - 2020年03月31日, 研究代表者本研究では新規に開発された細胞低接着性コラーゲン（Low Adhesive Scaffold Collagen：LASCol）による脊椎椎間板再生の可能性について検討した。ヒト椎間板細胞はLASCol上でのみ細胞凝集塊の形成と椎間板表現型・前駆細胞マーカーと細胞外基質の発現増大を示した。ラット椎間板髄核摘出モデルにLASColを埋植したところ、X線で椎間板高の維持、MRIで椎間板輝度の残存、さらに組織学的検討で椎間板表現型を有する細胞外基質産生細胞のLASCol内への浸潤を認めた。本研究結果からLASColが凝集塊の形成を介して組織再生の活性化を促す新たな椎間板再生材料となる可能性が示された。競争的資金
- 日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2015年04月01日 - 2019年03月31日椎間板研究にとって欠かせない、３種類の椎間板変性モデルを確立した。緩やかな変性を生じるモデルを用いて圧迫期間に伴い特に脊索由来細胞が早期に消失して非脊索由来細胞（軟骨様細胞を示唆）が相対的に増大していた。動的負荷培養装置を用いた実験では, 圧負荷により代表的なメカノレセプターであるintegrinの関与が椎間板変性に関与していることが明らかとなった。脊椎後方に小皮切から挿入可能なスペーサーを作成し、周辺機器も含めて改良を行い、有効性に関して大型動物実験を行い確認した。競争的資金
- 日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 神戸大学, 2016年04月01日 - 2018年03月31日, 研究代表者本研究の目的は細胞内伝達機構であるmTORシグナル経路の制御が脊椎椎間板の変性疾患の予防・治療法となる可能性を検証することであった。ヒト椎間板細胞に対するRNA干渉を用いたシグナル制御因子の解析から、mTORC1の抑制が椎間板保護作用を来すことを明らかにした。次にmTORC1阻害剤が類似の椎間板保護作用を来すことを確認した。さらにRNA干渉を用いてオートファジーの特異的な阻害を行い、オートファジーのアポトーシス細胞死とセネッセンス細胞老化の抑止効果を明らかとした。本研究結果から、mTORシグナル経路とオートファジーの制御が椎間板変性の新たな細胞生物学的予防・治療法となる可能性が示された。競争的資金
- 日本学術振興会, 科学研究費助成事業 基盤研究(C), 基盤研究(C), 神戸大学, 2015年04月01日 - 2018年03月31日ヒト椎間板髄核細胞にmTOR、Raptor、RictorのsiRNAを導入すると、全群でオートファジー活性が増加した。一方、RaptorのsiRNA導入群は他群に比べアポトーシスおよびセネッセンスに関連する酵素の発現が抑制されていた。Raptor の選択的な機能抑制がオートファジーの誘導とアポトーシス・老化・基質分解の抑制を来たしていると考えられた。実際に臨床で使用可能なmTOR阻害薬を使用してヒト椎間板髄核細胞への影響を検討したところ、多くに椎間板保護作用を認めたが、特にテムシロリムスは他剤に比べて親水性が高く、臨床上の投与方法にも利点があるため椎間板変性治療薬としての有用性が期待できる。競争的資金
- 一般社団法人 神緑会, 研究助成, 研究助成, 神戸大学, 2017年04月 - 2018年03月脊椎椎間板組織の恒常性維持におけるオートファジーの関与と役割の解明
- 公益財団法人 整形災害外科学研究助成財団, 研究助成, 大日本住友製薬奨励賞, 神戸大学, 2015年04月 - 2018年03月mTORシグナル経路の制御による椎間板変性治療法の開発
- 日本学術振興会, 科学研究費助成事業 若手研究(B), 若手研究(B), 神戸大学, 2014年04月01日 - 2017年03月31日椎間板変性の機序解明に向けて、①動的負荷が椎間板組織に与える影響、及び②椎間板変性とAdiponectinとの関係について調査した。①動的負荷を与えると椎間板変性は進行することが確認された。さらに、この動的刺激はメカノレセプターのIntegrin α5β1を介して椎間板細胞に伝達されることが確認された。本研究では、②adiponectin receptorが椎間板組織に発現していることを初めて明らかにできた。このadiponectin receptorは、椎間板変性動物モデルにおいて、変性ともに発現が減少していた。椎間板組織の恒常性の維持に関与しているものと考えられた。
- 日本学術振興会, 科学研究費助成事業 研究活動スタート支援, 研究活動スタート支援, 神戸大学, 2014年08月29日 - 2016年03月31日本研究の目的は、脊椎椎間板の変性過程におけるオートファジーの役割を明らかにし、その制御が椎間板変性の有効な治療法になりうるか検証することであった。まず、薬剤を用いたオートファジーの誘導が椎間板細胞保護作用を有することを確認した。さらに、保護作用を来すのに最も有用なオートファジー関連シグナル経路への干渉高位を特定した。動物を用いた検討でもオートファジー誘導剤の経口投与が椎間板組織の細胞外基質分解を抑制することを確認した。本研究結果から、オートファジーならびに関連するシグナル経路の制御が椎間板変性の新たな治療・予防法となる可能性が示唆された。得られた知見を基にさらに研究を進める所存である。
- 公益財団法人 上原記念生命科学財団, 海外留学助成, 海外留学助成, University of Pittsburgh, 2013年04月 - 2014年03月オートファジー制御による椎間板変性の抑制
- 一般社団法人 神緑会, 研究助成, 研究助成, 神戸大学, 2009年04月 - 2010年03月椎間板変性機序の解明と新たな治療戦略に関する研究
研究シーズ
■ 研究シーズ- 脊椎椎間板変性遺伝子・薬物治療法の開発研究キーワード：椎間板変性 , mTOR・オートファジー, 遺伝子・薬物治療, 脊椎, 整形外科研究の背景と目的：腰痛は非常に高い罹患率と就労困難などの莫大な社会経済学的負担から世界的な健康問題であり、脊椎の椎間板変性はその主たる要因とされています。椎間板の発生・解剖学的特徴から細胞内クリアランス機構であるオートファジーとその上流で制御を行うmTORシグナル経路が椎間板の恒常性維持に重要な役割を担っていると仮説を立て、研究を続けております。研究内容：mTORシグナルへの遺伝子干渉や類似の効果を示す薬剤の投与が関連シグナルやオートファジーの制御を介して椎間板変性への有効な治療法となる可能性を明らかにすべく、細胞・動物実験を行っております。これまでの細胞実験からmTORは細胞に必須のシグナル伝達経路である一方、mTOR複合体1（mTORC1）の選択的な抑制が椎間板変性抑止作用を示す可能性が示唆されました。そのため私どもの研究室で確立したラット椎間板変性モデルに対してmTORC1のみを抑制する遺伝子・薬物治療を行い、椎間板変性抑止効果の有無について現在検討を行っております。ラットなど小型動物実験での治療効果を基に、ウサギ・イヌ（軟骨異栄養性）など中・大型動物を用いた実験について、他大学との共同研究も視野に入れつつ検討していく予定です。期待される効果や応用分野：本法は細胞自身の清浄力・治癒力を高めることで椎間板の恒常性を維持して変性の進行を抑制する、より生理的な治療法・予防法となる可能性があり、本研究から得られた知見は脊椎椎間板（腰部脊柱管狭窄症）のみならず関節軟骨（変形性関節症）など多くの退行性疾患への繋がるものと考えられます。関係する業績：Kakiuchi Y, Yurube T, et al. Osteoarthritis Cartilage 27(6):965-76, 2019. Ito M, Yurube T, et al. Osteoarthritis Cartilage 25(12):2134-46, 2017. 科学研究費助成事業 26893151, 16K20051, 21K09323.
- 新規コラーゲンゲル充填剤を用いた脊椎椎間板組織修復の試み研究キーワード：椎間板変性 , 椎間板ヘルニア, LASCol, 脊椎, 整形外科研究の背景と目的：腰痛や関連した神経痛は世界的な健康問題であり、脊椎椎間板変性はその主たる要因とされています。破壊が進行した組織の再建には足場となる生体材料が重要になりますが、既存の材料では椎間板再生能に乏しく限界があり、新たな治療戦略が必要と考えるに至りました。そのため本研究では新規コラーゲンゲル充填剤による脊椎椎間板治療の可能性について検討しております。研究内容：本研究では近畿大学で開発された細胞低接着性コラーゲン（Low Adhesive Scaffold Collagen：LASCol）を用いた脊椎椎間板組織修復の可能性について検討しました。ヒト椎間板細胞はLASColゲル上でのみスフェロイド細胞凝集塊の形成ならびに椎間板表現型・前駆細胞マーカーと細胞外基質の発現増大を認めました。ラット椎間板髄核摘出モデルにLASColゲルを埋植したところ、X線撮影で椎間板高の維持、MRIで椎間板輝度の残存、組織学的検討で椎間板表現型を有する細胞外基質産生細胞のLASColゲル内への浸潤を認めました。以上よりLASColゲルがスフェロイド形成を介して細胞の活性化を促す新たな椎間板組織修復充填剤となる可能性が示されました。本研究結果を基に現在、近畿大学・神戸大学・大阪府立大学・神戸医療産業都市推進機構医療TRIの四者共同で共同研究を進めております。期待される効果や応用分野：LASColは単独で周囲から細胞を呼び込み凝集塊を形成することで微小環境の保持を可能とし、生体内に豊富に存在するコラーゲンを用いた、安全で安価な椎間板組織修復のための新規生体材料となる可能性が示唆されております。今回得られた知見から軟骨再生など他領域への応用が進み、変形性関節症の治療にも繋がる可能性があります。LASColを用いた低侵襲の再生医療の実現を目指して、今後も研究を継続して参ります。関係する業績：Takeoka Y, Yurube T, et al. Biomaterials 235:119781, 2020. 特願2019-569684「椎間板変性の治療剤および椎間板細胞培養剤」2021/10/19査定 令和2年度ACT-MS/AMED「ヘルニア・変性椎間板組織再生を促す新規コラーゲンゲル充填剤」 科学研究費助成事業 18K16659.