Research activity information

• Relationships between frailty and surgical outcomes of palliative surgery for spinal metastases : a prospective cohort study.

  Takeru Tsujimoto, Tomoya Matsuo, Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Ryosuke Kuroda, Kenichiro Kakutani

  AIMS: Frailty has recently been associated with postoperative complications and clinical outcomes in various fields. This study aimed to assess the relationships between frailty and surgical outcomes of palliative surgery for spinal metastases and assess the usefulness of the modified five-item frailty index (mFI-5) in this population. METHODS: We prospectively evaluated 273 patients who underwent spinal metastasis surgery from June 2015 to December 2021. The mFI-5 was used to assess frailty, with a score of 0 defined as non-frailty, 1 as pre-frailty, and 2 or more as frailty. The following variables were assessed: background characteristics, complications (Clavien-Dindo grade 2 or higher), postoperative clinical outcomes, and life expectancy. The clinical outcomes compared between the three groups were the performance status (PS), Barthel index, and EuroQoL five-dimension questionnaire (EQ-5D) at six months postoperatively. A multivariate stepwise logistic regression analysis was performed of variables with values of p < 0.1 on the univariate analysis. RESULTS: The overall complication rate was 19% (52/273). The complication rate was significantly higher in the frailty group (p = 0.005), and patients with a greater mFI-5 score tended to have a higher incidence of postoperative complications. The Kaplan-Meier curve showed that the non-frailty group had a significantly longer survival time than the pre-frailty and frailty groups (p < 0.001). Multivariate logistic regression analysis suggested that mFI-5 is not predictive of postoperative complications and improvement of the EQ-5D, while is predictive of improvement of the PS (odds ratio (OR) 4.22) and Barthel index (OR 4.49). CONCLUSION: The current study suggested that mFI-5 is not predictive of postoperative complications and improvement of the EQ-5D, while is predictive of improvement of the PS and Barthel index. Furthermore, palliative surgery for spinal metastases improved the PS, Barthel index, and EQ-5D, even in patients with frailty.

  Oct. 2025, Bone & joint open, 6(10) (10), 1199 - 1207, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Effectiveness of rehabilitation treatment for bone metastasis patients without surgical intervention: A propensity score matching analysis.

  Ryo Yoshikawa, Yasumitsu Fujii, Ryoga Kashima, Wataru Saho, Risa Harada, Daisuke Makiura, Katsuya Fujiwara, Junichiro Inoue, Yoshiki Takeoka, Ryoko Sawada, Naomasa Fukase, Keisuke Oe, Hitomi Hara, Kenichiro Kakutani, Toshihiro Akisue, Yoshitada Sakai

  Evidence regarding the effectiveness of rehabilitation treatments in patients with bone metastases remains limited. This study evaluated the implementation and effectiveness of rehabilitation in patients with bone metastases who did not undergo surgery. This retrospective study included 200 patients with nonsurgically treated bone metastases at our institution. The patients were categorized into a rehabilitation group (R group, n = 61) and a non-rehabilitation group (N group, n = 139). Over the course of one month, we compared activities of daily living (ADL), assessed using the Barthel Index (BI), quality of life (QOL), measured using the EuroQoL-5 Dimension (EQ-5D), and demographic and clinical characteristics. Propensity score matching was conducted to minimize selection bias. After matching, 31 patients in each group were included in the analysis. No statistically significant differences were observed in baseline BI and EQ-5D scores between the two groups. In the R group, BI improved significantly from 80 (interquartile range [IQR]: 60-100) to 90 (IQR: 70-100), and EQ-5D improved from 0.444 (IQR: 0.282-0.608) to 0.608 (IQR: 0.533-0.768). In contrast, no improvements were observed in either score in the N group. Chemotherapy was identified as a significant factor associated with improvements in BI (odds ratio 4.03) and EQ-5D (odds ratio 5.29). Rehabilitation may be a valuable treatment option for nonsurgically treated patients with bone metastases, warranting further validation in prospective studies.

  Aug. 2025, Journal of bone oncology, 53, 100703 - 100703, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Risk Factors for Wound Dehiscence After Spinal Metastasis Surgery and a New Approach to Prevention-Curved Skin Incision.

  Kunihiko Miyazaki, Yutaro Kanda, Takashi Yurube, Yoshiki Takeoka, Takeru Tsujimoto, Tomoya Matsuo, Masao Ryu, Naotoshi Kumagai, Kohei Kuroshima, Yoshiaki Hiranaka, Ryosuke Kuroda, Kenichiro Kakutani

  Background: Postoperative wound dehiscence is a major complication following spinal metastasis surgery, particularly in patients who receive preoperative radiotherapy or molecular-targeted therapy; however, preventive strategies remain limited. Objective: In this study, we aimed to identify the risk factors for postoperative wound dehiscence and evaluate the clinical utility of a novel curved skin incision (CSI) technique, designed to avoid irradiated areas, in comparison with the conventional midline incision (MI) technique. Methods: Logistic regression analysis was conducted on 107 patients who underwent MI between 2013 and 2018. Based on the results, we developed the CSI technique. Propensity score matching was performed to compare postoperative wound dehiscence in 29 matched pairs of patients treated with either CSI or MI from 2019 to 2021. Results: Preoperative radiotherapy and molecular-targeted therapy were found to be significant risk factors for wound dehiscence. CSI, which circumvents irradiated skin, was associated with a substantially lower rate of wound dehiscence than MI. Conclusions: The CSI technique offers a simple, reproducible, and effective surgical approach to reduce postoperative wound complications in high-risk patients. Its clinical benefit, especially for those with prior radiotherapy, suggests that it may serve as a valuable addition to standard spinal metastasis surgery.

  Jun. 2025, Cancers, 17(12) (12), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Transient Receptor Potential Vanilloid 4 Knockdown Decreases Extracellular Matrix Synthesis via Autophagy Suppression in the Rat Intervertebral Disc.

  Tomoya Matsuo, Yoshiki Takeoka, Takashi Yurube, Takeru Tsujimoto, Yutaro Kanda, Kunihiko Miyazaki, Hiroki Ohnishi, Masao Ryu, Naotoshi Kumagai, Kohei Kuroshima, Yoshiaki Hiranaka, Ryosuke Kuroda, Kenichiro Kakutani

  BACKGROUND: Transient receptor potential vanilloid 4 (TRPV4) has been identified as a Ca2+-permeable channel and is activated under physiological mechanical stimulation in disc nucleus pulposus (NP) cells. Meanwhile, the Ca2+-dependent AMP-activated protein kinase (AMPK)/mTOR pathway activates autophagy in notochordal cells. We hypothesized that TRPV4 is involved in the maintenance of intradiscal homeostasis via autophagy. Our objective was to elucidate the role of TRPV4 in extracellular matrix (ECM) metabolism and autophagy in the rat intervertebral disc through a loss-of-function study with the RNA interference (RNAi) technique. METHODS: In vitro study: Small interfering RNA (siRNA) was applied to knockdown TRPV4 by the reverse transfection method in rat disc NP cells. Expression of TRPV4, AMPK/mTOR pathway-related markers, and autophagy markers were measured by Western blotting (WB). Next, ECM metabolism was assessed under serum starvation and/or proinflammatory interleukin-1 beta (IL-1β) stimulation. In vivo study: TRPV4 and control siRNAs were injected into rat discs. To confirm in vivo transfection, WB for TRPV4 was conducted in rat disc NP-tissue protein extracts 2, 28, and 56 days after injection. Furthermore, 24-h temporary static compression-induced disruption of TRPV4 siRNA-injected discs was observed by radiography, histomorphology, and immunofluorescence. RESULTS: In vitro study: In disc cells, three different TRPV4 siRNAs consistently suppressed autophagy with TRPV4 protein knockdown (mean 33.2% [95% CI: -50.8, -15.5], 44.1% [-61.7, -26.4], 58.3% [-76.0, -40.7]). ECM metabolism was significantly suppressed by TRPV4 RNAi under proinflammatory IL-1β stimulation. In vivo study: The WB displayed sustained decreases in TRPV4 protein expression 2, 28, and 56 days after injection. Under the loaded condition, TRPV4 siRNA-injected discs presented radiographic height loss ([-31.7, -7.75]), histomorphological damage ([0.300, 4.70]), and immunofluorescent suppression of autophagy ([1.61, 20.5]) and ECM metabolism ([-25.2, -6.41]) compared to control siRNA-injected discs at 56 days. CONCLUSIONS: The TRPV4 could be a therapeutic target for intervertebral disc diseases via modulating autophagy.

  Mar. 2025, JOR spine, 8(1) (1), e70046, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Adulthood consequences of spinal deformity surgeries in neurofibromatosis type 1 patients.

  Arihiko Tsukamoto, Koki Uno, Teppei Suzuki, Masaaki Ito, Keita Nakashima, Kenichiro Kakutani, Yoshiki Takeoka

  BACKGROUND: Spinal deformity associated with Neurofibromatosis type1(NF-1) is known to be intractable, and it's surgical outcome is known to be poor. However, it is not clear whether or not patients are able to lead a healthy social life as adults, and we investigated the surgical outcomes of patients who had reached adulthood after surgery. METHODS: Thirty-eight patients (16 males, 22 females) who had undergone spinal deformity surgery and had reached the age of 18 years at last follow up were included. X-rays, surgery, complications, survival rate, employment status, and married rate were evaluated. HR-QOL was compared with those of adolescent idiopathic scoliosis(AIS) operated in our hospital. The idiopathic scoliosis group includes 110 patients who had undergone surgery from 2015 to 2018 at our hospital and 38 patients(2 males, 36 females) were selected by excluding patients who could not be followed up until the age of 18 years and those who did not describe their HR-QOL, and adjusting the mean preoperative cobb angle values to match those of the NF-1 group. RESULTS: The mean age at the initial surgery was 14.6 [4〜49] years, and the mean age at the last observation was 29.4 [18〜56] years. Anterior and posterior fusion were performed in 18 patients, posterior fixation was performed in 20 patients. Five patients died (3: malignant schwannoma, 1:brain tumor, 1:unknown), with a mean age of 27.0 [18〜35] years at the time of death and 12.2 [3〜21] years after the last surgery. Two patients over 40 years of age were treated for vascular system disorders, and 1 patient for a brain tumor. All survivors were ambulators except 1 case of non-ambulator due to neoplastic destruction of the hip joint. The working status was light work in 13 patients, desk work in 7, unemployed in 4, students in 8. Four patients were married. SRS-22 and ODI at the last follow-up in the NF-1 group and AIS group were compared. There were no significant differences in SRS-22 Pain, Mental Health, Satisfaction, and ODI, but SRS-22 Function and Self-image were significantly lower in the NF-1 group. CONCLUSIONS: At an average follow-up of 14.8 years after surgery, 5 of 38 patients had died, 29 patients (76.3%) were able to lead a social life. However, HR-QOL was lower than that of AIS. Patients undergoing NF-1 scoliosis surgery require careful long-term follow-up, taking into account the possibility of reoperation due to osteolysis, malignant changes in the tumor, and vascular problems due to vascular fragility.

  Feb. 2025, BMC musculoskeletal disorders, 26(1) (1), 113 - 113, English, International magazine

  Scientific journal


• Gene-Silencing Therapeutic Approaches Targeting PI3K/Akt/mTOR Signaling in Degenerative Intervertebral Disk Cells: An In Vitro Comparative Study Between RNA Interference and CRISPR-Cas9.

  Masao Ryu, Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Takeru Tsujimoto, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Naotoshi Kumagai, Kohei Kuroshima, Yoshiaki Hiranaka, Ryosuke Kuroda, Kenichiro Kakutani

  The mammalian target of rapamycin (mTOR), a serine/threonine kinase, promotes cell growth and inhibits autophagy. The following two complexes contain mTOR: mTORC1 with the regulatory associated protein of mTOR (RAPTOR) and mTORC2 with the rapamycin-insensitive companion of mTOR (RICTOR). The phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR signaling pathway is important in the intervertebral disk, which is the largest avascular, hypoxic, low-nutrient organ in the body. To examine gene-silencing therapeutic approaches targeting PI3K/Akt/mTOR signaling in degenerative disk cells, an in vitro comparative study was designed between small interfering RNA (siRNA)-mediated RNA interference (RNAi) and clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) gene editing. Surgically obtained human disk nucleus pulposus cells were transfected with a siRNA or CRISPR-Cas9 plasmid targeting mTOR, RAPTOR, or RICTOR. Both of the approaches specifically suppressed target protein expression; however, the 24-h transfection efficiency differed by 53.8-60.3% for RNAi and 88.1-89.3% for CRISPR-Cas9 (p < 0.0001). Targeting mTOR, RAPTOR, and RICTOR all induced autophagy and inhibited apoptosis, senescence, pyroptosis, and matrix catabolism, with the most prominent effects observed with RAPTOR CRISPR-Cas9. In the time-course analysis, the 168-h suppression ratio of RAPTOR protein expression was 83.2% by CRISPR-Cas9 but only 8.8% by RNAi. While RNAi facilitates transient gene knockdown, CRISPR-Cas9 provides extensive gene knockout. Our findings suggest that RAPTOR/mTORC1 is a potential therapeutic target for degenerative disk disease.

  Dec. 2024, Cells, 13(23) (23), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Modified Frailty Index as a novel predictor for the incidence and severity of postoperative complications after spinal metastases surgery.

  Tomoya Matsuo, Yutaro Kanda, Yoshitada Sakai, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Ryosuke Kuroda, Kenichiro Kakutani

  AIMS: Frailty has been gathering attention as a factor to predict surgical outcomes. However, the association of frailty with postoperative complications remains controversial in spinal metastases surgery. We therefore designed a prospective study to elucidate risk factors for postoperative complications with a focus on frailty. METHODS: We prospectively analyzed 241 patients with spinal metastasis who underwent palliative surgery from June 2015 to December 2021. Postoperative complications were assessed by the Clavien-Dindo classification; scores of ≥ Grade II were defined as complications. Data were collected regarding demographics (age, sex, BMI, and primary cancer) and preoperative clinical factors (new Katagiri score, Frankel grade, performance status, radiotherapy, chemotherapy, spinal instability neoplastic score, modified Frailty Index-11 (mFI), diabetes, and serum albumin levels). Univariate and multivariate analyses were developed to identify risk factors for postoperative complications (p < 0.05). RESULTS: Overall, 57 postoperative complications occurred in 47 of 241 (19.5%) patients. The most common complications were wound infection/dehiscence, urinary tract infection, and pneumonia. Univariate analysis identified preoperative radiotherapy (p = 0.028), mFI (p < 0.001), blood loss ≥ 500 ml (p = 0.016), and preoperative molecular targeted drugs (p = 0.030) as potential risk factors. From the receiver operating characteristic curve, the clinically optimal cut-off value of mFI was 0.27 (sensitivity, 46.8%; specificity, 79.9%). Multivariate analysis identified mFI ≥ 0.27 (odds ratio (OR) 2.94 (95% CI 1.44 to 5.98); p = 0.003) and preoperative radiotherapy (OR 2.11 (95% CI 1.00 to 4.46); p = 0.049) as significant risk factors. In particular, urinary tract infection (p = 0.012) and pneumonia (p = 0.037) were associated with mFI ≥ 0.27. Furthermore, the severity of postoperative complications was positively correlated with mFI (p < 0.001). CONCLUSION: The mFI is a useful tool to predict the incidence and the severity of postoperative complications in spinal metastases surgery.

  Dec. 2024, The bone & joint journal, 106-B(12) (12), 1469 - 1476, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• The Utility and Feasibility of Smart Glasses in Spine Surgery: Minimizing Radiation Exposure During Percutaneous Pedicle Screw Insertion.

  Yoshiaki Hiranaka, Yoshiki Takeoka, Takashi Yurube, Takeru Tsujimoto, Yutaro Kanda, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Naotoshi Kumagai, Kohei Kuroshima, Ryosuke Kuroda, Kenichiro Kakutani

  OBJECTIVE: Spine surgeons are often at risk of radiation exposure due to intraoperative fluoroscopy, leading to health concerns such as carcinogenesis. This is due to the increasing use of percutaneous pedicle screw (PPS) in spinal surgeries, resulting from the widespread adoption of minimally invasive spine stabilization. This study aimed to elucidate the effectiveness of smart glasses (SG) in PPS insertion under fluoroscopy. METHODS: SG were used as an alternative screen for fluoroscopic images. Operators A (2-year experience in spine surgery) and B (9-year experience) inserted the PPS into the bilateral L1-5 pedicles of the lumbar model bone under fluoroscopic guidance, repeating this procedure twice with and without SG (groups SG and N-SG, respectively). Each vertebral body's insertion time, radiation dose, and radiation exposure time were measured, and the deviation in screw trajectories was evaluated. RESULTS: The groups SG and N-SG showed no significant difference in insertion time for the overall procedure and each operator. However, group SG had a significantly shorter radiation exposure time than group N-SG for the overall procedure (109.1 ± 43.5 seconds vs. 150.9 ± 38.7 seconds; p = 0.003) and operator A (100.0 ± 29.0 seconds vs. 157.9 ± 42.8 seconds; p = 0.003). The radiation dose was also significantly lower in group SG than in group N-SG for the overall procedure (1.3 ± 0.6 mGy vs. 1.7 ± 0.5 mGy; p = 0.023) and operator A (1.2 ± 0.4 mGy vs. 1.8 ± 0.5 mGy; p = 0.013). The 2 groups showed no significant difference in screw deviation. CONCLUSION: The application of SG in fluoroscopic imaging for PPS insertion holds potential as a useful method for reducing radiation exposure.

  Jun. 2024, Neurospine, 21(2) (2), 432 - 439, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Predictors of Persistent Postoperative Numbness Following Lumbar Fusion in Patients Older Than 75 Years: A Minimum 2-Year Follow-up.

  Takeru Tsujimoto, Masahiro Kanayama, Shotaro Fukada, Fumihiro Oha, Yukitoshi Shimamura, Yuichi Hasegawa, Tomoyuki Hashimoto, Kenichiro Kakutani, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Norimasa Iwasaki

  OBJECTIVE: To evaluate the preoperative and perioperative predictors of persistent leg numbness following lumbar fusion in patients aged ≥ 75 years. METHODS: This single-center retrospective study examined 304 patients aged ≥ 75 years who underwent lumbar fusion for lumbar degenerative disease (102 men, 202 women; mean age, 79.2 [75-90] years). The visual analogue scale (VAS) score for leg numbness was examined preoperatively and at 2 years postoperatively. The persistent leg numbness group included patients with a 2-year postoperative VAS score for leg numbness ≥ 5 points. The demographic data were also reviewed. A multivariate stepwise logistic regression analysis was performed for variables with univariate analysis values of p < 0.2 on univariate analysis. RESULTS: In total, 71 patients (23.4%) experienced persistent postoperative leg numbness. Multivariate logistic regression analysis revealed that a history of lumbar decompression, longer symptom duration, and a preoperative VAS score for leg numbness ≥ 5 points were associated with greater postoperative persistent leg numbness following lumbar fusion. In contrast, other factors, such as sex, body mass index, vertebral fracture, diabetes mellitus, depression, symptom duration, dural injury, operative time, and estimated blood loss, were not. CONCLUSION: A history of preoperative lumbar decompression, longer symptom duration, and greater preoperative VAS scores for leg numbness were preoperative predictors of persistent postoperative leg numbness following lumbar fusion in older patients. Although lumbar fusion is expected to improve leg numbness, surgeons should consider the surgical history, duration, and preoperative numbness intensity and explain the potential postoperative persistent leg numbness in advance.

  Jun. 2024, Neurospine, 21(2) (2), 596 - 605, English, International magazine

  Scientific journal


• Evaluation of Changes in Activities of Daily Living and Quality of Life of Patients with Bone Metastasis Who Underwent Conservative Therapy through Bone Metastasis Cancer Boards.

  Yasumitsu Fujii, Ryo Yoshikawa, Ryoga Kashima, Wataru Saho, Hirokazu Onishi, Tsuyoshi Matsumoto, Risa Harada, Yoshiki Takeoka, Ryoko Sawada, Naomasa Fukase, Hitomi Hara, Kenichiro Kakutani, Toshihiro Akisue, Yoshitada Sakai

  Background and Objectives: Changes in activities of daily living (ADL) and quality of life (QOL) of patients with bone metastasis who underwent surgical treatment through Bone Metastasis Cancer Boards (BMCBs), a recent multidisciplinary approach for managing bone metastases, have been reported; however, no reports exist on patients who undergo conservative treatment. In this study, we aimed to evaluate these patients' ADL and QOL and examine the factors influencing changes in these parameters. Materials and Methods: We retrospectively reviewed 200 patients with bone metastases who underwent conservative therapy through BMCBs between 2013 and 2021. A reassessment was conducted within 2-8 weeks after the initial assessment. Patients' background and changes in performance status (PS), Barthel Index (BI), EuroQol five-dimension (EQ-5D) scores, and Numerical Rating Scale (NRS) scores were initially assessed. Furthermore, we categorized patients into two groups based on improvements or deteriorations in ADL and QOL and performed comparative analyses. Results: Significant improvements in EQ-5D (0.57 ± 0.02 versus [vs.] 0.64 ± 0.02), NRS max (5.21 ± 0.24 vs. 3.56 ± 0.21), and NRS average (2.98 ± 0.18 vs. 1.85 ± 0.13) scores were observed between the initial assessment and reassessment (all p < 0.001). PS (1.84 ± 0.08 vs. 1.72 ± 0.08) and BI (83.15 ± 1.68 vs. 84.42 ± 1.73) also showed improvements (p = 0.06, and 0.054, respectively). In addition, spinal cord paralysis (odds ratio [OR]: 3.69, p = 0.049; OR: 8.42, p < 0.001), chemotherapy (OR: 0.43, p = 0.02; OR: 0.25, p = 0.007), and NRS average scores (OR: 0.38, p = 0.02; OR: 0.14, p < 0.001) were independent factors associated with ADL and QOL. Conclusions: Patients with bone metastases who underwent conservative treatment through BMCBs exhibited an increase in QOL without a decline in ADL. The presence of spinal cord paralysis, absence of chemotherapy, and poor pain control were associated with a higher risk of deterioration in ADL and QOL.

  May 2024, Medicina (Kaunas, Lithuania), 60(6) (6), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Two-Staged Surgery for Kyphoscoliosis in Larsen Syndrome with A 30-Year Follow-Up: A Case Report.

  Masahiko Furuya, Yoshiki Takeoka, Takashi Yurube, Masaaki Ito, Teppei Suzuki, Kenichiro Kakutani, Koki Uno

  May 2024, Spine surgery and related research, 8(3) (3), 338 - 341, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 脊椎転移手術における原発巣悪性度別手術成績比較

  大西 洋輝, 神田 裕太郎, 由留部 崇, 武岡 由樹, 辻本 武尊, 酒井 良忠, 秋末 敏宏, 黒田 良祐, 角谷 賢一朗

  (公社)日本整形外科学会, Mar. 2024, 日本整形外科学会雑誌, 98(3) (3), S1250 - S1250, Japanese


• Clinical Characteristics, Surgical Outcomes, and Risk Factors for Emergency Surgery in Patients With Spinal Metastases: A Prospective Cohort Study.

  Yutaro Kanda, Kenichiro Kakutani, Yoshitada Sakai, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Naotoshi Kumagai, Kohei Kuroshima, Yoshiaki Hiranaka, Ryosuke Kuroda

  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.

  Mar. 2024, Neurospine, 21(1) (1), 314 - 327, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Bidirectionally validated in silico and in vitro formation of specific depth zone-derived chondrocyte spheroids and clusters.

  Eiichiro Takada, Hayato L Mizuno, Yoshiki Takeoka, Shuichi Mizuno

  3D multicellular self-organized cluster models, e.g., organoids are promising tools for developing new therapeutic modalities including gene and cell therapies, pharmacological mechanistic and screening assays. Various applications of these models have been used extensively for decades, however, the mechanisms of cluster formation, maintenance, and degradation of these models are not even known over in-vitro-life-time. To explore such advantageous models mimicking native tissues or organs, it is necessary to understand aforementioned mechanisms. Herein, we intend to clarify the mechanisms of the formation of cell clusters. We previously demonstrated that primary chondrocytes isolated from distinct longitudinal depth zones in articular cartilage formed zone-specific spherical multicellular clusters in vitro. To elucidate the mechanisms of such cluster formation, we simulated it using the computational Cellular Potts Model with parameters were translated from gene expression levels and histological characteristics corresponding to interactions between cell and extracellular matrix. This simulation in silico was validated morphologically with cluster formation in vitro and vice versa. Since zone specific chondrocyte cluster models in silico showed similarity with corresponding in vitro model, the in silico has a potential to be used for prediction of the 3D multicellular in vitro models used for development, disease, and therapeutic models.

  2024, Frontiers in bioengineering and biotechnology, 12, 1440434 - 1440434, English, International magazine

  Scientific journal


• Effect of Bone Metastasis Cancer Board on Spinal Surgery Outcomes: A Retrospective Study.

  Kunihiko Miyazaki, Yutaro Kanda, Yoshitada Sakai, Ryo Yoshikawa, Takashi Yurube, Yoshiki Takeoka, Hitomi Hara, Toshihiro Akisue, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Nov. 2023, Medicina (Kaunas, Lithuania), 59(12) (12), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 骨転移患者に対するリハビリテーション治療効果 傾向スコアマッチングを用いた検討

  吉川 遼, 藤井 康光, 大西 宏和, 津田 悠三, 中村 謙, 鹿島 遼河, 佐保 航, 原田 理沙, 武岡 由樹, 澤田 良子, 深瀬 直政, 原 仁美, 角谷 賢一朗, 秋末 敏宏, 黒田 良祐, 酒井 良忠

  (公社)日本リハビリテーション医学会, Oct. 2023, The Japanese Journal of Rehabilitation Medicine, 60(秋季特別号) (秋季特別号), S355 - S355, Japanese


• 認定健康スポーツナースの救護活動に関する教育プログラム開発についての文献的考察

  峯山 佳恵, 葛西 好美, 中村 摩紀, 上田 雄也, 島 稔樹, 元野 紘平, 高島 良典, 武岡 由樹, 黒田 良祐

  (一社)日本臨床スポーツ医学会, Oct. 2023, 日本臨床スポーツ医学会誌, 31(4) (4), S232 - S232, Japanese


• Clinical Characteristics and Surgical Outcomes of Metastatic Spine Tumors in the Very Elderly: A Prospective Cohort Study in a Super-Aged Society.

  Yutaro Kanda, Kenichiro Kakutani, Yoshitada Sakai, Kunihiko Miyazaki, Tomoya Matsuo, Takashi Yurube, Yoshiki Takeoka, Hiroki Ohnishi, Masao Ryu, Naotoshi Kumagai, Kohei Kuroshima, Yoshiaki Hiranaka, Teruya Kawamoto, Hitomi Hara, Yuichi Hoshino, Shinya Hayashi, Toshihiro Akisue, Ryosuke Kuroda

  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.

  Jul. 2023, Journal of clinical medicine, 12(14) (14), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Intervertebral disc cell fate during aging and degeneration: apoptosis, senescence, and autophagy.

  Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Jun. 2023, North American Spine Society journal, 14, 100210 - 100210, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Preoperative Base Excess as a Predictor of Perioperative Complications in Patients with Nonidiopathic Scoliosis who Have High Risk Associated with General Anesthesia.

  Yutaro Kanda, Kenichiro Kakutani, Moritoki Egi, Zhongying Zhang, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Yuichi Hoshino, Ryosuke Kuroda

  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.

  May 2023, Spine surgery and related research, 7(3) (3), 268 - 275, English, Domestic magazine

  Scientific journal


• Regenerative Capability of Human Nucleus Pulposus Cells in Degenerated Disc Under Hydrostatic Pressure Mimicking Physiologically Relevant Intradiscal Pressure In Vitro.

  Yoshiki Takeoka, Yutaro Kanda, James D Kang, Shuichi Mizuno

  STUDY DESIGN: Isolated human nucleus pulposus (hNP) cells from the degenerated intervertebral disc (IVD) were incubated under hydrostatic pressure (HP) and evaluated for regenerative potential. OBJECTIVES: To characterize metabolic turnover in hNP cells isolated from degenerated IVDs classified by Pfirrmann grade under physiologically relevant HP at high osmolality in vitro. SUMMARY OF BACKGROUND DATA: We demonstrated that bovine caudal nucleus pulposus cells isolated from healthy cows produced more extracellular matrix under cyclic HP followed by constant pressure (mimicking physiological intradiscal pressure in humans) than under no pressure in vitro. We assessed the effects of pressure on human degenerated cells isolated under the same regimen of pressure used for bovine cells. MATERIALS AND METHODS: hNP cells isolated from discarded tissue classified as Pfirrmann grade 2 to 3 (n = 13: age, 46.7 ± 14.0) and grade 4 (n = 13: age, 53.0 ± 11.5) were incubated under cyclic HP at 0.2 to 0.7 MPa, 0.5 Hz for 2 days followed by constant pressure at 0.3 MPa for 1 day, repeated twice over 6 days. The gene expression and immunohistology of matrix molecules and catabolic and anticatabolic proteins were evaluated. RESULTS: Aggrecan and collagen type II expression were significantly more upregulated under HP in grades 2 to 3 than in grade 4 tissues (both, P < 0.01). Linear regression analysis showed a positive correlation between matrix metalloproteinase 13 and tissue inhibitor for metalloproteinase 2 expression in grades 2 to 3, whereas a negative correlation was found in grade 4 ( P < 0.05). Immunohistological staining revealed the activation of a mechanoreceptor, transient receptor potential vanilloid 4, under HP. CONCLUSIONS: Resident cells in mild-moderate degenerated discs classified as Pfirrmann grade 2 to 3 have the potential to promote extracellular matrix production and maintain adequate cell viability under physiological spinal loading. RELEVANCE: This study explored the potential of degenerated remnant nucleus pulposus cells under a physiological environment, possibly leading to establishing strategies for IVD regeneration.

  May 2023, Spine, 48(10) (10), 728 - 736, English, International magazine

  Scientific journal


• Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration.

  Hiroki Ohnishi, Zhongying Zhang, Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Ryu Tsujimoto, Kunihiko Miyazaki, Tomoya Matsuo, Masao Ryu, Naotoshi Kumagai, Kohei Kuroshima, Yoshiaki Hiranaka, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  May 2023, International journal of molecular sciences, 24(10) (10), English, International magazine

  Scientific journal


• 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 Curved skin incision

  宮崎 邦彦, 神田 裕太郎, 武岡 由樹, 張 鍾穎, 由留部 崇, 大西 洋輝, 松尾 智哉, 劉 正夫, 秋末 敏宏, 黒田 良祐, 角谷 賢一朗

  (公社)日本整形外科学会, Mar. 2023, 日本整形外科学会雑誌, 97(2) (2), S289 - S289, Japanese


• The Identification of Risk Factors for Symptomatic Spinal Metastasis Onset: A Prospective Cohort Study of 128 Asymptomatic Spinal Metastasis Patients.

  Kenichiro Kakutani, Yutaro Kanda, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Kohei Kuroshima, Naotoshi Kumagai, Yoshiaki Hiranaka, Shinya Hayashi, Yuichi Hoshino, Hitomi Hara, Yoshitada Sakai, Ryosuke Kuroda

  Background: Symptomatic spinal metastasis (SSM) decreases the activities of daily living (ADL) and quality of life of cancer patients. However, the risk factors for SSM onset remain unclear. This prospective cohort study aimed to statistically analyze the significant risk factors. Methods: From 2016 to 2018, 210 consecutive patients with spinal metastases were prospectively registered. Patients with SSM at the first consultation and those who were unable to be followed-up owing to poor general condition were excluded. The demographic factors (age, sex, primary cancer, performance status, and ADL), clinical factors (radiation therapy, chemotherapy, molecularly targeted drugs, and bone-modifying agents (BMAs)), and Spinal Neoplastic Instability Score (SINS) were evaluated. Multivariate analysis was performed to identify the risk factors for SSM onset. Furthermore, the threshold was calculated from the receiver operating characteristic curve using the Youden index. Results: Thirty-nine patients who presented with SSM at the first consultation and 43 patients who were unable to be followed-up owing to poor general condition were excluded. Finally, 128 asymptomatic patients were included. Thirty-seven patients (28.9%) developed SSM during the follow-up period. The total SINS (OR: 1.739; 95% CI: 1.345-2.250) was identified as the most significant factor. The cut-off value of the SINS was 9.5 (sensitivity: 67.6%; specificity: 83.5%). Twenty-five (62.5%) of the forty patients with a SINS ≥ 10 developed SSM within a mean of 5.5 months (95% CI: 1.17-9.83). Furthermore, all patients with a SINS ≥ 13 developed SSM (n = 5) within a mean of 1.37 months (95% CI: 0.0-3.01). Conclusions: This study identified the significant risk factors for SSM onset and the threshold of the SINS. If long-term survival is expected, patients with a SINS ≥ 10 should be considered for intervention to prevent SSM.

  Feb. 2023, Cancers, 15(4) (4), English, International magazine

  Scientific journal


• The Combination of Separation Surgery and Intensity Modulated Radiation Therapy (IMRT) for a Primary Osteosarcoma of the Spine: A Case Report and Literature Review.

  Yutaro Kanda, Yuji Kakiuchi, Takashi Yurube, Yoshiki Takeoka, Kunihiko Miyazaki, Ryosuke Kuroda, Kenichiro Kakutani

  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, Clinical medicine insights. Case reports, 16, 11795476231171891 - 11795476231171891, English, International magazine


• Survival Rate after Palliative Surgery Alone for Symptomatic Spinal Metastases: A Prospective Cohort Study.

  Kenichiro Kakutani, Yoshitada Sakai, Zhongying Zhang, Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Kunihiko Miyazaki, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Kohei Kuroshima, Naotoshi Kumagai, Yoshiaki Hiranaka, Shinya Hayashi, Yuichi Hoshino, Hitomi Hara, Ryosuke Kuroda

  The effect of spine surgery for symptomatic spinal metastases (SSM) on patient prognosis remains unclear. This study aimed to reveal the prognosis of patients with SSM after spine surgery. One hundred twenty-two patients with SSM were enrolled in this prospective cohort study. The patients who received chemotherapy after enrollment were excluded. The decision of surgery depended on patient's willingness; the final cohort comprised 31 and 24 patients in the surgery and non-surgery groups, respectively. The patients were evaluated by their performance status (PS), activities of daily living (ADL) and ambulatory status. Survival was evaluated by the Kaplan-Meier method. The PS, ADL and ambulation were significantly improved in the surgery group compared to non-surgery group. The median survival was significantly longer in the surgery group (5.17 months, 95% confidence interval (CI) 3.27 to 7.07) than in the non-surgery group (2.23 months, 95% CI 2.03 to 2.43; p = 0.003). Furthermore, the patients with a better PS, ADL and ambulatory status had a significantly longer survival. Surgery improved the PS, ADL, ambulation and survival of patients with SSM. In the management of SSM, spine surgery is not only palliative but may also prolong survival.

  Oct. 2022, Journal of clinical medicine, 11(21) (21), English, International magazine

  Scientific journal


• 「空手道大会救護実践セミナー」開催における満足度・理解度調査と今後の課題

  峯山 佳恵, 上田 雄也, 島 稔樹, 元野 紘平, 高島 良典, 武岡 由樹, 黒田 良祐

  (一社)日本臨床スポーツ医学会, Oct. 2022, 日本臨床スポーツ医学会誌, 30(4) (4), S225 - S225, Japanese


• Protective Effects of Growth Differentiation Factor-6 on the Intervertebral Disc: An In Vitro and In Vivo Study.

  Kunihiko Miyazaki, Shingo Miyazaki, Takashi Yurube, Yoshiki Takeoka, Yutaro Kanda, Zhongying Zhang, Yuji Kakiuchi, Ryu Tsujimoto, Hiroki Ohnishi, Tomoya Matsuo, Masao Ryu, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Mar. 2022, Cells, 11(7) (7), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Improved Accuracy and Safety of Pedicle Screw Placement by Using a Probe with an Electrical Conductivity-Measuring Device during Severe Syndromic and Neuromuscular Scoliosis Spine Surgery.

  Takashi Yurube, Yutaro Kanda, Masaaki Ito, Yoshiki Takeoka, Teppei Suzuki, Koki Uno, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Jan. 2022, Journal of clinical medicine, 11(2) (2), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Complications of Posterior Fusion for Atlantoaxial Instability in Children With Down Syndrome

  Yoshiki Takeoka, Kenichiro Kakutani, Hiroshi Miyamoto, Teppei Suzuki, Takashi Yurube, Izumi Komoto, Masao Ryu, Shinichi Satsuma, Koki Uno

  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, Dec. 2021, Neurospine, 18(4) (4), 778 - 785

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Multidisciplinary Treatment for Spinal Metastases

  角谷 賢一朗, 張 鐘穎, 由留部 崇, 垣内 裕司, 武岡 由樹, 酒井 良忠, 秋末 敏宏, 黒田 良祐

  株式会社医学書院, Oct. 2021, 臨床整形外科, 56(10) (10), 1231 - 1237


• Involvement of Atg5-dependent autophagy in the maintenance of rat intervertebral disc homeostasis: in-vitro and in-vivo study

  TAKEOKA Yoshiki

  THE CENTRAL JAPAN ASSOCIATION OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY, Sep. 2021, The Central Japan Journal of Orthopaedic Surgery & Traumatology, 64(5) (5), 615 - 616, Japanese


• Delayed notochordal cell disappearance through integrin α5β1 mechanotransduction during ex-vivo dynamic loading-induced intervertebral disc degeneration.

  Yutaro Kanda, Takashi Yurube, Yusuke Morita, Yoshiki Takeoka, Takuto Kurakawa, Ryu Tsujimoto, Kunihiko Miyazaki, Yuji Kakiuchi, Shingo Miyazaki, Zhongying Zhang, Toru Takada, Yuichi Hoshino, Koichi Masuda, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Sep. 2021, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 39(9) (9), 1933 - 1944, English, International magazine

  Scientific journal


• Surgical outcomes and risk factors for poor outcomes in patients with cervical spine metastasis: a prospective study.

  Yutaro Kanda, Kenichiro Kakutani, Yoshitada Sakai, Zhongying Zhang, Takashi Yurube, Shingo Miyazaki, Yuji Kakiuchi, Yoshiki Takeoka, Ryu Tsujimoto, Kunihiko Miyazaki, Hiroki Ohnishi, Yuichi Hoshino, Toru Takada, Ryosuke Kuroda

  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.

  Jul. 2021, Journal of orthopaedic surgery and research, 16(1) (1), 423 - 423, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Augmented Chondroitin Sulfate Proteoglycan Has Therapeutic Potential for Intervertebral Disc Degeneration by Stimulating Anabolic Turnover in Bovine Nucleus Pulposus Cells under Changes in Hydrostatic Pressure.

  Yoshiki Takeoka, Phani Paladugu, James D Kang, Shuichi Mizuno

  Nucleus pulposus (NP) cells are exposed to changes in hydrostatic pressure (HP) and osmotic pressure within the intervertebral disc. We focused on main disc matrix components, chondroitin sulfate proteoglycan (CSPG) and hyaluronan (HA) to elucidate the capability of augmented CSPG to enhance the anabolism of bovine NP (bNP) cells under repetitive changes in HP at high osmolality. Aggrecan expression with CSPG in the absence of HP was significantly upregulated compared to the no-material control (phosphate buffer saline) under no HP at 3 days, and aggrecan expression with CSPG under HP was significantly higher than the control with HA under HP at 12 days. Collagen type I expression under no HP was significantly lower with CSPG than in controls at 3 days. Although matrix metalloproteinase 13 expression under HP was downregulated compared to no HP, it was significantly greater with HA than the control and CSPG, even under HP. Immunohistology revealed the involvement of mechanoreceptor of transient receptor potential vanilloid-4 activation under HP, suggesting an HP transduction mechanism. Addition of CSPG had anabolic and anti-fibrotic effects on bNP cells during the early culture period under no HP; furthermore, it showed synergy with dynamic HP to increase bNP-cell anabolism at later time points.

  Jun. 2021, International journal of molecular sciences, 22(11) (11), English, International magazine

  Scientific journal


• Commentary on "Intraoperative Monitoring for Cauda Equina Tumors: Surgical Outcomes and Neurophysiological Data Accrued Over 10 Years".

  Yoshiki Takeoka

  Jun. 2021, Neurospine, 18(2) (2), 290 - 291, English, International magazine


• Development of a standardized histopathology scoring system for intervertebral disc degeneration and regeneration in rabbit models-An initiative of the ORSspine section.

  Sarah E Gullbrand, Beth G Ashinsky, Alon Lai, Jennifer Gansau, James Crowley, Carla Cunha, Julie B Engiles, Marion Fusellier, Carol Muehleman, Matthew Pelletier, Steven Presciutti, Jordy Schol, Yoshiki Takeoka, Takashi Yurube, Yejia Zhang, Koichi Masuda, James C Iatridis

  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.

  Jun. 2021, JOR spine, 4(2) (2), e1147, English, International magazine

  Scientific journal


• Development of a standardized histopathology scoring system for intervertebral disc degeneration in rat models: An initiative of the ORS spine section.

  Alon Lai, Jennifer Gansau, Sarah E Gullbrand, James Crowley, Carla Cunha, Stefan Dudli, Julie B Engiles, Marion Fusellier, Raquel M Goncalves, Daisuke Nakashima, Jeffrey Okewunmi, Matthew Pelletier, Steven M Presciutti, Jordy Schol, Yoshiki Takeoka, Sidong Yang, Takashi Yurube, Yejia Zhang, James C Iatridis

  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.

  Jun. 2021, JOR spine, 4(2) (2), e1150, English, International magazine

  Scientific journal


• Inhibition of Autophagy at Different Stages by ATG5 Knockdown and Chloroquine Supplementation Enhances Consistent Human Disc Cellular Apoptosis and Senescence Induction rather than Extracellular Matrix Catabolism.

  Masaaki Ito, Takashi Yurube, Yutaro Kanda, Yuji Kakiuchi, Yoshiki Takeoka, Toru Takada, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Apr. 2021, International journal of molecular sciences, 22(8) (8), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• A novel topical treatment for bone metastases using a gelatin hydrogel incorporating cisplatin as a sustained release system.

  Yutaro Kanda, Kenichiro Kakutani, Takashi Yurube, Zhongying Zhang, Shingo Miyazaki, Yuji Kakiuchi, Yoshiki Takeoka, Ryu Tsujimoto, Kunihiko Miyazaki, Teruya Kawamoto, Toru Takada, Yuichi Hoshino, Yasuhiko Tabata, Ryosuke Kuroda

  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.

  Mar. 2021, Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 39(3) (3), 525 - 535, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• In vitro nucleus pulposus tissue model with physicochemical stresses.

  Yoshiki Takeoka, James D Kang, Shuichi Mizuno

  Intervertebral discs (IVDs) are exposed to changes in physicochemical stresses including hydrostatic and osmotic pressure via diurnal spinal motion. Homeostasis, degeneration, and regeneration in IVDs have been studied using in vitro, ex vivo, and animal models. However, incubation of nucleus pulposus (NP) cells in medium has limited capability to reproduce anabolic turnover and regeneration under physicochemical stresses. We developed a novel pressure/perfusion cell culture system and a semipermeable membrane pouch device for enclosing isolated NP cells for in vitro incubation under physicochemical stresses. We assessed the performance of this system to identify an appropriate stress loading regimen to promote gene expression and consistent accumulation of extracellular matrices by bovine caudal NP cells. Cyclic hydrostatic pressure (HP) for 4 days followed by constant HP for 3 days in high osmolality (HO; 450 mOsm/kg H2O) showed a trend towards upregulated aggrecan expression and dense accumulation of keratan sulfate without gaps by the NP cells. Furthermore, a repetitive regimen of cyclic HP for 2 days followed by constant HP for 1 day in HO (repeated twice) significantly upregulated gene expression of aggrecan (P < .05) compared to no pressure and suppressed matrix metalloproteinase-13 expression (P < .05) at 6 days. Our culture system and pouches will be useful to reproduce physicochemical stresses in NP cells for simulating anabolic, catabolic, and homeostatic turnover under diurnal spinal motion.

  Sep. 2020, JOR spine, 3(3) (3), e1105, English, International magazine

  Scientific journal


• 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

  神田 裕太郎, 角谷 賢一朗, 酒井 良忠, 由留部 崇, 張 鍾穎, 垣内 裕司, 武岡 由樹, 辻本 龍, 宮崎 邦彦, 宮崎 真吾, 高田 徹, 黒田 良祐

  (公社)日本整形外科学会, Jul. 2020, 日本整形外科学会雑誌, 94(6) (6), S1528 - S1528, Japanese


• 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

  神田 裕太郎, 角谷 賢一朗, 酒井 良忠, 由留部 崇, 垣内 裕司, 武岡 由樹, 辻本 龍, 河本 旭哉, 原 仁美, 秋末 敏宏, 黒田 良祐

  (公社)日本リハビリテーション医学会, Jul. 2020, The Japanese Journal of Rehabilitation Medicine, 57(特別号) (特別号), 3 - 2, Japanese


• 頸椎転移の手術成績と成績不良因子の検討

  神田 裕太郎, 角谷 賢一朗, 酒井 良忠, 張 鍾穎, 由留部 崇, 垣内 裕司, 武岡 由樹, 辻本 龍, 宮崎 邦彦, 高田 徹, 黒田 良祐

  (公社)日本整形外科学会, Mar. 2020, 日本整形外科学会雑誌, 94(3) (3), S1096 - S1096, Japanese


• 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

  神田 裕太郎, 角谷 賢一朗, 酒井 良忠, 張 鍾穎, 由留部 崇, 垣内 裕司, 武岡 由樹, 辻本 龍, 宮崎 邦彦, 宮崎 真吾, 高田 徹, 黒田 良祐

  (一社)日本脊椎脊髄病学会, Mar. 2020, Journal of Spine Research, 11(3) (3), 221 - 221, Japanese


• Reduced nucleotomy-induced intervertebral disc disruption through spontaneous spheroid formation by the Low Adhesive Scaffold Collagen (LASCol).

  Yoshiki Takeoka, Takashi Yurube, Koichi Morimoto, Saori Kunii, Yutaro Kanda, Ryu Tsujimoto, Yohei Kawakami, Naomasa Fukase, Toshiyuki Takemori, Kaoru Omae, Yuji Kakiuchi, Shingo Miyazaki, Kenichiro Kakutani, Toru Takada, Kotaro Nishida, Masanori Fukushima, Ryosuke Kuroda

  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.

  Mar. 2020, Biomaterials, 235, 119781 - 119781, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Improved bone bonding of hydroxyapatite spacers with a high porosity in a quantitative computed tomography-image pixel analysis: A prospective 1-year comparative study of the consecutive cohort undergoing double-door cervical laminoplasty.

  Yoshiki Takeoka, Takashi Yurube, Koichiro Maeno, Yutaro Kanda, Ryu Tsujimoto, Kunihiko Miyazaki, Yuji Kakiuchi, Shingo Miyazaki, Zhongying Zhang, Toru Takada, Kotaro Nishida, Minoru Doita, Ryosuke Kuroda, Kenichiro Kakutani

  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.

  Mar. 2020, JOR spine, 3(1) (1), e1080, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Gene Therapy Approach for Intervertebral Disc Degeneration: An Update.

  Yoshiki Takeoka, Takashi Yurube, Kotaro Nishida

  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.

  Mar. 2020, Neurospine, 17(1) (1), 3 - 14, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Pharmacological inhibition of mTORC1 but not mTORC2 protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism through Akt and autophagy induction.

  Y Kakiuchi, T Yurube, K Kakutani, T Takada, M Ito, Y Takeoka, Y Kanda, S Miyazaki, R Kuroda, K Nishida

  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.

  Jun. 2019, Osteoarthritis and cartilage, 27(6) (6), 965 - 976, English, International magazine

  [Refereed]

  Scientific journal


• 脊椎転移に対する手術療法の効果と限界

  角谷 賢一朗, 酒井 良忠, 由留部 崇, 高田 徹, 張 鍾頴, 宮崎 真吾, 垣内 裕司, 武岡 由樹, 神田 祐太郎, 辻本 龍, 河本 旭哉, 原 仁美, 深瀬 直政, 岡田 卓也, 坂下 明大, 佐々木 良平, 秋末 敏宏, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, May 2019, Journal of Spine Research, 10(5) (5), 898 - 904, Japanese


• 椎間板研究の最前線 椎間板変性治療 オートファジー

  由留部 崇, 伊藤 雅明, 垣内 裕司, 角谷 賢一朗, 高田 徹, 武岡 由樹, 神田 裕太郎, 辻本 龍, 宮崎 真吾, 張 鍾穎, 黒田 良祐, 西田 康太郎

  (株)医学書院, Nov. 2018, 臨床整形外科, 53(11) (11), 975 - 980, Japanese

  [Refereed]


• 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

  伊藤雅明, Yurube Takashi, 垣内裕司, 武岡由樹, 神田裕太郎, Kakutani Kenichiro, 高田徹, Kuroda Ryosuke, Nishida Kotaro

  (一社)日本脊椎脊髄病学会, Sep. 2018, Journal of Spine Research, 9(9) (9), 1388 - 1393, Japanese

  [Refereed]

  Scientific journal


• 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

  神田 裕太郎, 角谷 賢一朗, 由留部 崇, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 高田 徹, 田畑 泰彦, 土井田 稔, 西田 康太郎, 黒田 良祐

  (公社)日本整形外科学会, Aug. 2018, 日本整形外科学会雑誌, 92(8) (8), S1809 - S1809, Japanese

  [Refereed]


• 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

  竹森 俊幸, 深瀬 直政, 森本 康一, 國井 沙織, 由留部 崇, 武岡 由樹, 河本 旭哉, 新倉 隆宏, 原 仁美, 秋末 敏宏, 黒田 良祐

  (公社)日本整形外科学会, Aug. 2018, 日本整形外科学会雑誌, 92(8) (8), S1999 - S1999, Japanese


• Postoperative Walking Ability of Non-ambulatory Cervical Myelopathy Patients.

  Yoshiki Takeoka, Shuichi Kaneyama, Masatoshi Sumi, Koichi Kasahara, Aritetsu Kanemura, Masato Takabatake, Hiroaki Hirata, Masanori Tsubosaka

  STUDY DESIGN: A retrospective analysis. OBJECTIVE: The aim of this study was to clarify the postoperative improvement of walking ability and prognostic factors in nonambulatory patients with cervical myelopathy. SUMMARY OF BACKGROUND DATA: Many researchers have reported the surgical outcome in compressive cervical myelopathy. However, regarding severe gait disturbance,, it has not been clarified yet how much improvement can be expected. METHODS: One hundred thirty-one nonambulatory patients with cervical myelopathy were treated surgically and followed for an average of 3 years. Walking ability was graded according to the lower-extremity function subscore (L/E subscore) in Japanese Orthopedic Association score. We divided patients based on preoperative L/E subscores: group A, L/E subscore of 1 point (71 patients); and group B, 0 or 0.5 point (60 patients). The postoperative walking ability was graded by L/E subscore: excellent, ≥2 points; good, 1.5 points; fair, 1 point; and poor, 0.5 or 0 points. We compared preoperative and postoperative scores. The cutoff value of disease duration providing excellent improvement was investigated. RESULTS: Overall, 50 patients were graded as excellent (38.2%), and 21 patients were graded as good (16.0%). In group B, 17 patients (28.3%) were graded as excellent. Seventeen patients who were graded as excellent had shorter durations of myelopathic symptoms and/or gait disturbance (7.9 and 3.8 months respectively) than the others (29.5 and 8.9 months, respectively) (P < 0.05). Receiver-operating characteristic curve showed that the optimal cutoff values of the duration of myelopathic symptoms and gait disturbance providing excellent improvement were 3 and 2 months, respectively. CONCLUSION: Even if the patients were nonambulatory, 28.3% of them became able to walk without support after operation. If a patient becomes nonambulatory within 3 months from the onset of myelopathy or 2 months from the onset of gait disturbance, surgical treatment should be performed immediately to raise the possibility to improve stable gait. LEVEL OF EVIDENCE: 3.

  Aug. 2018, Spine, 43(16) (16), E927-E934, English, International magazine

  Scientific journal


• 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

  竹森 俊幸, 深瀬 直政, 森本 康一, 國井 沙織, 由留部 崇, 武岡 由樹, 原 仁美, 河本 旭哉, 黒田 良祐, 秋末 敏宏

  (公社)日本リハビリテーション医学会, May 2018, The Japanese Journal of Rehabilitation Medicine, 55(特別号) (特別号), 1 - 6, Japanese


• Selective interference of mTORC1/RAPTOR protects against human disc cellular apoptosis, senescence, and extracellular matrix catabolism with Akt and autophagy induction.

  M Ito, T Yurube, K Kakutani, K Maeno, T Takada, Y Terashima, Y Kakiuchi, Y Takeoka, S Miyazaki, R Kuroda, K Nishida

  Dec. 2017, Osteoarthritis and cartilage, 25(12) (12), 2134 - 2146, English, International magazine

  [Refereed]

  Scientific journal


• The Influence of Joint Distraction Force on the Soft-Tissue Balance Using Modified Gap-Balancing Technique in Posterior-Stabilized Total Knee Arthroplasty.

  Kanto Nagai, Hirotsugu Muratsu, Yoshiki Takeoka, Masanori Tsubosaka, Ryosuke Kuroda, Tomoyuki Matsumoto

  BACKGROUND: During modified gap-balancing technique, there is no consensus on the best method for obtaining appropriate soft-tissue balance and determining the femoral component rotation. METHODS: Sixty-five varus osteoarthritic patients underwent primary posterior-stabilized total knee arthroplasty using modified gap-balancing technique. The influence of joint distraction force on the soft-tissue balance measurement during the modified gap-balancing technique was evaluated with Offset Repo-Tensor between the osteotomized surfaces at extension, and between femoral posterior condyles and tibial osteotomized surface at flexion of the knee before the resection of femoral posterior condyles. The joint center gap (millimeters) and varus ligament balance (°) were measured under 20, 40, and 60 pounds of joint distraction forces, and the differences in these values at extension and flexion (the value at flexion minus the value at extension) were also calculated. RESULTS: The differences in joint center gap (-6.7, -6.8, and -6.9 mm for 20, 40, and 60 pounds, respectively) and varus ligament balance (3.5°, 3.8°, and 3.8°) at extension and flexion were not significantly different among different joint distraction forces, although the joint center gap and varus ligament balance significantly increased stepwise at extension and flexion as the joint distraction force increased. CONCLUSION: The difference in joint center gap and varus ligament balance at extension and flexion were consistent even among the different joint distraction forces. This novel index would be useful for the determination of femoral component rotation during the modified gap-balancing technique.

  Oct. 2017, The Journal of arthroplasty, 32(10) (10), 2995 - 2999, English, International magazine

  Scientific journal


• Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study.

  Shingo Miyazaki, Kenichiro Kakutani, Yoshitada Sakai, Yasuo Ejima, Koichiro Maeno, Toru Takada, Takashi Yurube, Yoshiki Terashima, Masaaki Ito, Yuji Kakiuchi, Yoshiki Takeoka, Hitomi Hara, Teruya Kawamoto, Akihiro Sakashita, Takuya Okada, Naomi Kiyota, Yoshiyuki Kizawa, Ryohei Sasaki, Toshihiro Akisue, Hironobu Minami, Ryosuke Kuroda, Kotaro Nishida

  PURPOSE: Palliative surgery for patients with spinal metastasis provides good clinical outcomes. However, there have been few studies on quality of life (QOL) and cost-utility of this surgery. We aimed to elucidate QOL and cost-utility of surgical treatment for spinal metastasis. METHODS: We prospectively analyzed 47 patients with spinal metastasis from 2010 to 2014 who had a surgical indication. Thirty-one patients who desired surgery underwent spinal surgery (surgery group). Sixteen patients who did not want to undergo spinal surgery (non-surgery group). The EuroQol 5D (EQ-5D) and relevant costs were measured at one, three, six, and 12 months after study enrollment. Health state values were obtained by Japanese EQ-5D scoring and quality-adjusted life years (QALY) gained were calculated for each group. Cost-utility was expressed as the incremental cost-utility ratio (ICUR). RESULTS: Health state values improved from 0.036 at study enrollment to 0.448 at 12 months in the surgery group, but deteriorated from 0.056 to 0.019 in the non-surgery group, with a significant difference between groups (P < 0.05). The mean QALY gained at 12 months were 0.433 in the surgery group and 0.024 in the non-surgery group. The mean total cost per patient in the surgery group was $25,770 compared with $8615 in the non-surgery group. The ICUR using oneyear follow-up data was $42,003/QALY gained. CONCLUSIONS: Surgical treatment for spinal metastases is associated with significant improvement in health state value. In orthopaedic surgery, an ICUR less than $50,000/QALY gained is considered acceptable cost-effectiveness. Our results indicate that surgical treatment could be cost-effective.

  Jun. 2017, International orthopaedics, 41(6) (6), 1265 - 1271, English, International magazine

  Scientific journal


• 脊椎転移に対する集学的治療の予後改善効果

  角谷 賢一朗, 酒井 良忠, 前野 耕一郎, 高田 徹, 由留部 崇, 寺島 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 江島 泰生, 原 仁美, 岡田 卓也, 坂下 明大, 佐々木 良平, 秋末 敏宏, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Feb. 2017, Journal of Spine Research, 8(2) (2), 139 - 146, Japanese


• 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.

  Yoshiki Terashima, Kenichiro Kakutani, Takashi Yurube, Toru Takada, Koichiro Maeno, Hiroaki Hirata, Shingo Miyazaki, Masaaki Ito, Yuji Kakiuchi, Yoshiki Takeoka, Ryosuke Kuroda, Kotaro Nishida

  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.

  Nov. 2016, Journal of orthopaedic surgery and research, 11(1) (1), 147 - 147, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 椎間板変性の病態解明 椎間板変性モデルについて

  Nishida Kotaro, 由留部崇, 高田徹, Kakutani Kenichiro, Maeno Koichiro, 伊藤雅明, 寺嶋良樹, 垣内裕司, 武岡由樹

  (公社)日本整形外科学会, Aug. 2016, 日本整形外科学会雑誌, 90(8) (8), S1659 - S1659, Japanese

  [Refereed]

  Research society


• A new predictive indicator by arthrography for future acetabular growth following conservative treatment of developmental dysplasia of the hip.

  Shinichi Satsuma, Daisuke Kobayashi, Maki Kinugasa, Yoshiki Takeoka, Ryosuke Kuroda, Masahiro Kurosaka

  The aim of this study was to find a new predictive indicator for acetabular growth of developmental dysplasia of the hip. Seventy-three hips that were diagnosed with developmental dysplasia of the hip and treated by conservative reduction were included in our study. In 30 hips with center-edge angle ≤ 10° at age 4, the center-edge of the acetabular limbus angle (CEALA) in the arthrogram was measured. On the basis of the results, CEALA was significantly smaller in the secondary acetabular dysplasia group than in the normal group at maturity. In conclusion, CEALA is a more reliable and accurate predictive indicator for acetabular development than center-edge angle or acetabular index.

  May 2016, Journal of pediatric orthopedics. Part B, 25(3) (3), 207 - 11, English, International magazine

  Scientific journal

• 脊椎転移手術における悪性度別手術成績比較

  大西 洋輝, 角谷 賢一朗, 由留部 崇, 武岡 由樹, 神田 裕太郎, 宮崎 邦彦, 平中 良明, 酒井 良忠, 秋末 敏宏, 黒田 良祐

  (公社)日本整形外科学会, Jun. 2023, 日本整形外科学会雑誌, 97(6) (6), S1352 - S1352, Japanese


• 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

  由留部 崇, 垣内 裕司, 角谷 賢一朗, 高田 徹, 田所 浩, 武岡 由樹, 神田 裕太郎, 辻本 龍, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Sep. 2019, 日本整形外科学会雑誌, 93(8) (8), S1645 - S1645, Japanese


• 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

  辻本 龍, 由留部 崇, 垣内 裕司, 角谷 賢一朗, 高田 徹, 武岡 由樹, 神田 裕太郎, 宮崎 真吾, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Sep. 2019, 日本整形外科学会雑誌, 93(8) (8), S1649 - S1649, Japanese


• 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

  由留部 崇, 伊藤 雅明, 垣内 裕司, 角谷 賢一朗, 高田 徹, 田所 浩, 武岡 由樹, 辻本 龍, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Sep. 2019, 日本整形外科学会雑誌, 93(8) (8), S1798 - S1798, Japanese


• 「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

  由留部 崇, 渡邉 信佳, 角谷 賢一朗, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 黒田 良祐

  (公社)日本リハビリテーション医学会, May 2019, The Japanese Journal of Rehabilitation Medicine, 56(特別号) (特別号), 3 - 3, Japanese


• 「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

  由留部 崇, 渡邉 信佳, 角谷 賢一朗, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 黒田 良祐

  (公社)日本リハビリテーション医学会, May 2019, The Japanese Journal of Rehabilitation Medicine, 56(特別号) (特別号), 3 - 14, Japanese


• 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

  角谷 賢一朗, 酒井 良忠, 由留部 崇, 高田 徹, 張 鐘穎, 宮崎 真吾, 垣内 裕司, 武岡 由樹, 神田 祐太郎, 辻本 龍, 黒田 良祐, 西田 康太郎

  日本外科系連合学会, May 2019, 日本外科系連合学会誌, 44(3) (3), 534 - 534, Japanese


• The Effectiveness and Limitation of Spine Surgery for Spinal Metastasis

  角谷 賢一朗, 酒井 良忠, 由留部 崇, 高田 徹, 張 鍾頴, 宮崎 真吾, 垣内 裕司, 武岡 由樹, 神田 祐太郎, 辻本 龍, 河本 旭哉, 原 仁美, 深瀬 直政, 岡田 卓也, 坂下 明大, 佐々木 良平, 秋末 敏宏, 黒田 良祐, 西田 康太郎

  日本脊椎脊髄病学会, May 2019, Journal of spine research : official journal of the Japanese Society for Spine Surgery and Related Research, 10(5) (5), 898 - 904, Japanese


• 骨転移Cancer Boardの効果と課題

  角谷 賢一朗, 酒井 良忠, 由留部 崇, 高田 徹, 張 鐘穎, 宮崎 真吾, 垣内 裕司, 武岡 由樹, 神田 祐太郎, 辻本 龍, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 670 - 670, Japanese


• 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

  由留部 崇, 角谷 賢一朗, 宇野 耕吉, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 宮崎 真吾, 張 鍾穎, 高田 徹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 210 - 210, Japanese


• 筋ジストロフィーに伴う脊柱変形の手術経験

  角谷 賢一朗, 由留部 崇, 張 鐘穎, 宮崎 真吾, 高田 徹, 垣内 裕司, 武岡 由樹, 神田 祐太郎, 辻本 龍, 鈴木 哲平, 蔵川 拓外, 宇野 耕吉, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 318 - 318, Japanese


• 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

  由留部 崇, 垣内 裕司, 伊藤 雅明, 角谷 賢一朗, 高田 徹, 田所 浩, 武岡 由樹, 神田 裕太郎, 辻本 龍, 宮崎 真吾, 張 鍾穎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 609 - 609, Japanese


• 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

  高田 徹, 角谷 賢一朗, 由留部 崇, 張 鍾穎, 宮崎 真吾, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 644 - 644, Japanese


• 脊椎転移手術における早期成績不良例に関する検討

  張 鍾穎, 角谷 賢一朗, 由留部 崇, 宮崎 真吾, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 高田 徹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 668 - 668, Japanese


• 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

  垣内 裕司, 由留部 崇, 角谷 賢一朗, 高田 徹, 武岡 由樹, 神田 裕太郎, 辻本 龍, 宮崎 真吾, 張 鍾穎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 679 - 679, Japanese


• 「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

  由留部 崇, 竹岡 亨, 渡邉 信佳, 稲岡 秀陽, 角谷 賢一朗, 高田 徹, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 宮崎 真吾, 張 鍾穎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2019, Journal of Spine Research, 10(3) (3), 702 - 702, Japanese


• 脊椎転移の症候化リスク因子に関する前向き研究

  角谷 賢一朗, 酒井 良忠, 由留部 崇, 高田 徹, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 西田 康太郎, 黒田 良祐

  (公社)日本整形外科学会, Mar. 2019, 日本整形外科学会雑誌, 93(3) (3), S1073 - S1073, Japanese


• 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

  由留部 崇, 渡邉 信佳, 角谷 賢一朗, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 辻本 龍, 黒田 良祐

  (公社)日本リハビリテーション医学会, Oct. 2018, The Japanese Journal of Rehabilitation Medicine, 55(秋季特別号) (秋季特別号), S299 - S299, Japanese


• 70歳以上の脊椎転移患者の手術成績 PS、ADL、QOLの推移から

  神田 裕太郎, 角谷 賢一朗, 酒井 良忠, 河本 旭哉, 原 仁美, 深瀬 直政, 辻本 龍, 武岡 由樹, 垣内 裕司, 由留部 崇, 秋末 敏宏, 黒田 良祐

  (公社)日本リハビリテーション医学会, Oct. 2018, The Japanese Journal of Rehabilitation Medicine, 55(秋季特別号) (秋季特別号), S274 - S274, Japanese


• 脊椎転移の症候化リスク因子の前向き検討

  神田 裕太郎, 角谷 賢一朗, 酒井 良忠, 河本 旭哉, 原 仁美, 深瀬 直政, 辻本 龍, 武岡 由樹, 垣内 裕司, 由留部 崇, 秋末 敏宏, 黒田 良祐

  (公社)日本リハビリテーション医学会, Oct. 2018, The Japanese Journal of Rehabilitation Medicine, 55(秋季特別号) (秋季特別号), S367 - S367, Japanese


• 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

  垣内 裕司, 由留部 崇, 角谷 賢一朗, 高田 徹, 伊藤 雅明, 武岡 由樹, 神田 裕太郎, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Aug. 2018, 日本整形外科学会雑誌, 92(8) (8), S1881 - S1881, Japanese


• 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

  武岡 由樹, 由留部 崇, 森本 康一, 國井 沙織, 深瀬 直政, 竹森 俊幸, 垣内 裕司, 角谷 賢一朗, 高田 徹, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Aug. 2018, 日本整形外科学会雑誌, 92(8) (8), S1733 - S1733, Japanese


• 動的圧迫負荷が、integrinα5β1を介して脊索由来細胞に与える影響

  神田 裕太郎, 角谷 賢一朗, 森田 有亮, 由留部 崇, 垣内 裕司, 武岡 由樹, 蔵川 拓外, 高田 徹, 土井田 稔, 西田 康太郎, 黒田 良祐

  (公社)日本整形外科学会, Aug. 2018, 日本整形外科学会雑誌, 92(8) (8), S1775 - S1775, Japanese


• 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

  由留部 崇, 垣内 裕司, 武岡 由樹, 角谷 賢一朗, 高田 徹, 伊藤 雅明, 神田 裕太郎, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Aug. 2018, 日本整形外科学会雑誌, 92(8) (8), S1775 - S1775, Japanese


• 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

  由留部 崇, 伊藤 雅明, 渡邉 信佳, 竹岡 亨, 角谷 賢一朗, 高田 徹, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Mar. 2018, 日本整形外科学会雑誌, 92(3) (3), S632 - S632, Japanese


• 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

  武岡 由樹, 由留部 崇, 國井 沙織, 森本 康一, 深瀬 直政, 竹森 俊幸, 垣内 裕司, 伊藤 雅明, 神田 裕太郎, 角谷 賢一朗, 高田 徹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 233 - 233, Japanese


• 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

  由留部 崇, 伊藤 雅明, 渡邉 信佳, 竹岡 亨, 角谷 賢一朗, 高田 徹, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 378 - 378, Japanese


• 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

  高田 徹, 角谷 賢一朗, 由留部 崇, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 478 - 478, Japanese


• 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

  神田 裕太郎, 角谷 賢一朗, 森田 有亮, 由留部 崇, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 蔵川 拓外, 寺嶋 良樹, 高田 徹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 537 - 537, Japanese


• 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

  伊藤 雅明, 由留部 崇, 角谷 賢一朗, 高田 徹, 垣内 裕司, 武岡 由樹, 神田 裕太郎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 539 - 539, Japanese


• 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

  垣内 裕司, 由留部 崇, 角谷 賢一朗, 高田 徹, 伊藤 雅明, 武岡 由樹, 神田 裕太郎, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 540 - 540, Japanese


• 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

  西田 康太郎, 由留部 崇, 角谷 賢一朗, 高田 徹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 神田 祐太郎, 黒田 良祐

  (一社)日本脊椎脊髄病学会, Mar. 2018, Journal of Spine Research, 9(3) (3), 602 - 602, Japanese


• 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

  垣内 裕司, 由留部 崇, 角谷 賢一朗, 高田 徹, 伊藤 雅明, 武岡 由樹, 神田 裕太郎, 黒田 良祐, 西田 康太郎

  (一社)日本移植学会, Feb. 2018, 移植, 52(6) (6), 587 - 587, Japanese


• 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

  森本康一, 國井沙織, 武岡由樹, 由留部崇, 加藤暢宏, 尾前薫, 黒田良祐

  日本バイオマテリアル学会, 2018, 日本バイオマテリアル学会大会予稿集(Web), 40th, 216 - 216, Japanese


• 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

  武岡由樹, 由留部崇, 國井沙織, 森本康一, 竹森俊幸, 深瀬直政, 垣内裕司, 角谷賢一朗, 黒田良祐

  2018, Japanese Journal of Rehabilitation Medicine, 55(Supplement) (Supplement)


• 脊椎転移に対する集学的治療は予後を延長させる

  角谷賢一朗, 酒井良忠, 由留部崇, 高田徹, 伊藤雅明, 垣内裕司, 武岡由樹, 神田祐太郎, 秋末敏宏, 河本旭哉, 原仁美, 黒田良祐, 西田康太郎

  2018, Journal of Spine Research, 9(3) (3)


• 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

  竹森俊幸, 深瀬直政, 森本康一, 國井沙織, 由留部崇, 武岡由樹, 河本旭哉, 河本旭哉, 新倉隆宏, 原仁美, 秋末敏宏, 秋末敏宏, 黒田良祐

  2018, 日本整形外科学会雑誌, 92(8) (8)


• 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

  伊藤 雅明, 由留部 崇, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 垣内 裕司, 武岡 由樹, 土井田 稔, 黒田 良祐, 西田 健太郎

  (公社)日本整形外科学会, Aug. 2017, 日本整形外科学会雑誌, 91(8) (8), S1488 - S1488, Japanese


• 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

  由留部 崇, 伊藤 雅明, 寺嶋 良樹, 垣内 裕司, 武岡 由樹, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Aug. 2017, 日本整形外科学会雑誌, 91(8) (8), S1489 - S1489, Japanese


• 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

  垣内 裕司, 由留部 崇, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 伊藤 雅明, 武岡 由樹, 土井田 稔, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Aug. 2017, 日本整形外科学会雑誌, 91(8) (8), S1691 - S1691, Japanese


• 症候性脊椎転移の発生リスクに関する前向き研究

  角谷 賢一朗, 酒井 良忠, 河本 旭哉, 高田 徹, 前野 耕一郎, 由留部 崇, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 原 仁美, 深瀬 直政, 秋末 敏宏, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Jun. 2017, 日本整形外科学会雑誌, 91(6) (6), S1408 - S1408, Japanese


• 症候性脊椎転移の発生リスクに関する前向き研究

  角谷 賢一朗, 酒井 良忠, 高田 徹, 前野 耕一郎, 由留部 崇, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 485 - 485, Japanese


• 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

  由留部 崇, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 酒井 良忠, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 663 - 663, Japanese


• 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

  西田 康太郎, 高田 徹, 角谷 賢一朗, 由留部 崇, 前野 耕一郎, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 黒田 良祐

  (公社)日本整形外科学会, Mar. 2017, 日本整形外科学会雑誌, 91(2) (2), S132 - S132, Japanese


• 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

  伊藤 雅明, 由留部 崇, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 垣内 裕司, 武岡 由樹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 296 - 296, Japanese


• 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

  垣内 裕司, 由留部 崇, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 伊藤 雅明, 武岡 由樹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 296 - 296, Japanese


• 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?

  西田 康太郎, 角谷 賢一朗, 由留部 崇, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 黒田 良祐

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 322 - 322, Japanese


• 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

  由留部 崇, 伊藤 雅明, 垣内 裕司, 寺嶋 良樹, 武岡 由樹, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 589 - 589, Japanese


• 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

  角谷 賢一朗, 宇野 耕吉, 由留部 崇, 前野 耕一郎, 高田 徹, 鈴木 哲平, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 黒田 良祐, 西田 康太郎

  (一社)日本脊椎脊髄病学会, Mar. 2017, Journal of Spine Research, 8(3) (3), 779 - 779, Japanese


• 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

  由留部 崇, 角谷 賢一朗, 前野 耕一郎, 高田 徹, 寺嶋 良樹, 伊藤 雅明, 垣内 裕司, 武岡 由樹, 酒井 良忠, 黒田 良祐, 西田 康太郎

  (公社)日本整形外科学会, Mar. 2017, 日本整形外科学会雑誌, 91(2) (2), S606 - S606, Japanese

• Research on a treatment system for degenerative intervertebral discs using silk elastin - Attempts to create artificial intervertebral discs -

  角谷 賢一朗, 由留部 崇, 辻本 武尊, 武岡 由樹, 神田 裕太郎, 田畑 泰彦, 西田 英高

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Scientific Research (B), Kobe University, 01 Apr. 2025 - 31 Mar. 2029


• メカノレセプターTRPV4を介した椎間板内恒常性維持機構の解明

  武岡 由樹

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 01 Apr. 2025 - 31 Mar. 2028


• 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

  張 鍾穎, 由留部 崇, 角谷 賢一朗, 武岡 由樹

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 01 Apr. 2023 - 31 Mar. 2026

  椎間板変性は腰痛の主な原因の一つである。アディポネクチンは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り、抗炎症作用を有すると報告されている。また、アディポネクチンはAdipoR1やAdipoR2といった受容体に結合してその作用を発揮し、それら受容体の発現量が増強するとアディポネクチンの作用も増強することが報告されている。我々は過去に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を用いてアディポネクチンが椎間板の炎症や変性へ及ぼす影響を調査し、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を報告した。アディポネクチンの臨床応用を目指し、今回はまず始めに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の作用機序を明らかにするための実験を行うこととした。脊椎手術を施行された20～70歳代14例のヒト椎間板細胞を培養して6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、アディポロン＋IL-1β+AdipoR1 SiRNA投与群: A+I+R1 Si群、アディポロン＋IL-1β+AdipoR2 SiRNA投与群: A+I+R2 Si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や炎症経路のタンパク発現をRT-PCR,蛍光免疫染色、Western Blotting法を用いて調査することを計画した。RT-PCR法でTNF-α、IL-6、MMP-13、ADAMTS-4についてI群とA+I群間では有意に発現低下を認めたが、A+I群とA+I+R1 Si群やA+I+R2 Si群の間には有意差は認めていない。蛍光免疫染色とWestern Blotting法でも同様の結果となっている。


• メカノレセプターTRPV4による椎間板変性に対する治療アプローチ

  武岡 由樹

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 01 Apr. 2022 - 31 Mar. 2025

• 椎間板変性の治療剤および椎間板細胞培養材

  由留部 崇, 武岡 由樹, 森本 康一, 國井 沙織, 尾前 薫

  JP2019003494, 31 Jan. 2019, 国立大学法人神戸大学, 学校法人近畿大学, 公益財団法人神戸医療産業都市推進機構, WO2019-151444, 08 Aug. 2019

  Patent right

  IRI