Research activity information

• Lumbar ossification of the posterior longitudinal ligament as a distinct phenotype of diffuse spinal ligament ossification1.
  Yoshinao Koike; Tsutomu Endo; Ryo Fujita; Katsuhisa Yamada; Masahiro Kanayama; Hideki Sudo; Ken Kadoya; Huohuo Xue; M Alaa Terkawi; Daisuke Ukeba; Takashi Ohnishi; Shotaro Fukada; Yohei Sodeyama; Ryota Suzuki; Misaki Ishii; Norimasa Iwasaki
  The spine journal : official journal of the North American Spine Society, 03 Feb. 2026, [International Magazine]
  English, Scientific journal, BACKGROUND CONTEXT: Lumbar ossification of the posterior longitudinal ligament (L-OPLL) has been underrecognized and remains poorly characterized clinically. We hypothesized that L-OPLL constitutes a distinct phenotype within the broader OPLL spectrum, sharing features of obesity and diffuse spinal ligament ossification. PURPOSE: To evaluate the clinical and radiographic features of L-OPLL and assess their relationship with diffuse spinal ligament ossification and obesity-related factors. STUDY DESIGN: Cross-sectional study with a replication cohort. PATIENT SAMPLE: A total of 186 patients with OPLL were diagnosed using whole-spine computed tomography (CT) at a regional spine center in Japan (2007-2024). Additionally, 75 asymptomatic individuals with OPLL from a population-based health screening cohort comprised the replication cohort. OUTCOME MEASURES: Patient background, including BMI, was assessed. Spinal ligament ossification was evaluated using whole-spine CT. The severity of ossification was scored for four ligaments-OPLL, OALL (ossification of the anterior longitudinal ligament), OLF (ossification of the ligamentum flavum), and ossification of the supra/interspinous ligament-and summed to define the ossification index (OS index). Regional scores from the cervical, thoracic, and lumbar spine were combined to calculate the total index. METHODS: In the primary analysis, patients were classified into L-OPLL and non-L-OPLL groups, and their clinical and radiographic features were compared. Multiple linear regression analysis was used to assess the independent association between L-OPLL and OS index. In the secondary analysis, patients were classified into three groups: localized cervical OPLL (C-OPLL), thoracic OPLL (T-OPLL), and L-OPLL groups, and comparisons were made between the localized C-OPLL group and the T- and L-OPLL groups. RESULTS: The L-OPLL group had a significantly higher BMI (median 27.5 vs. 26.0 kg/m², p=0.003) and greater prevalence of obesity than the non-L-OPLL group, along with significantly elevated thoracic OPLL and OLF indices. Multiple linear regression analysis confirmed that L-OPLL was independently associated with a higher OS index (regression coefficient: 0.448, 95% confidence interval: 0.162 to 0.735, p=0.002). The L-OPLL group also exhibited significantly higher BMI and OS index than the localized C-OPLL group, primarily driven by increased thoracic and lumbar OPLL and OLF. The replication cohort results were consistent with an association between L-OPLL, obesity, and diffuse ligament ossification. CONCLUSIONS: L-OPLL is rarely an isolated lumbar lesion; instead, it commonly coexists with extensive spinal ligament ossification and marked obesity. Its distinct clinical and radiographic features support classification as a separate entity within the broader OPLL spectrum.
• Editorial: Macrophages: allies or merciless enemies in musculoskeletal systems
  M. Alaa Terkawi; Ken Kadoya; Tsutomu Endo
  Frontiers in Immunology, 16, Frontiers Media SA, 16 Dec. 2025
  Scientific journal
• Transcriptomic profiling reveals a dramatic inflammatory shift in osteal macrophages during colitis-induced osteoporosis.
  Ryota Suzuki; Liyile Chen; Tsutomu Endo; Taiki Tokuhiro; Masaya Nakajo; Yuki Ogawa; Hend Alhasan; Taku Ebata; Daisuke Takahashi; Ken Kadoya; Masahiko Takahata; Norimasa Iwasaki; M Alaa Terkawi
  Inflammation research : official journal of the European Histamine Research Society ... [et al.], 74, 1, 165, 165, 21 Nov. 2025, [International Magazine]
  English, Scientific journal, OBJECTIVE: Colitis disrupts the intestinal barrier, leading to increased permeability and the translocation of harmful microbial components into the circulation and distant organs, including bone. Given that macrophages serve as both frontline immune defenders in tissues and key regulators of bone homeostasis, this study investigates molecular alterations in osteal macrophages (Omacs) and their contribution to bone loss in a murine model of colitis-induced osteoporosis. METHODS: Colitis-induced osteoporosis was established by administering DSS in drinking water for 5 days. Omacs were isolated from bone tissue and subjected to bulk RNA-seq analysis, phagocytosis assays and co-culture models with osteoblasts or osteoclast precursors. RESULTS: RNA-seq data of Omcas demonstrated a shift towards an inflammatory phenotype under colitis conditions, which was accompanied by bone loss in mice. The upregulated genes in these cells were most significantly enriched in IL-17, NF-κB, and TNF signaling pathways. Importantly, these cells exhibited decreased phagocytic activity and were able to disrupt osteoblast differentiation and promote osteoclast differentiation in vitro. CONCLUSIONS: These results indicate that colitis triggers a significant inflammatory response in Omacs, which can contribute to bone metabolic dysfunction. Modulating the activation of inflammatory pathways may offer a potential therapeutic avenue for treating colitis-induced osteoporosis.
• Efferocytosis at the frontline of homeostasis: Shaping the bone microenvironment and therapeutic implications in related diseases
  Liyile Chen; Ken Kadoya; Endo Tsutomu; Norimasa Iwasaki; M Alaa Terkawi
  Cytokine & Growth Factor Reviews, Elsevier BV, May 2025
  Scientific journal
• Therapeutic Potential of Targeting Ferroptosis in Periprosthetic Osteolysis Induced by Ultra-High-Molecular-Weight Polyethylene Wear Debris
  Takuya Ogawa; Shunichi Yokota; Liyile Chen; Yuki Ogawa; Yoshio Nishida; Taiki Tokuhiro; Hend Alhasan; Tomoyo Yutani; Tomohiro Shimizu; Daisuke Takahashi; Takuji Miyazaki; Tsutomu Endo; Ken Kadoya; Mohamad Alaa Terkawi; Norimasa Iwasaki
  Biomedicines, 13, 1, 170, 170, MDPI AG, 13 Jan. 2025
  Scientific journal, Background/Objectives: Periprosthetic osteolysis is the primary cause of arthroplasty failure in the majority of patients. Mechanistically, wear debris released from the articulating surfaces of a prosthesis initiates local inflammation and several modes of regulated cell death programs, such as ferroptosis, which represents a promising therapeutic target in various chronic inflammatory diseases. Thus, the current study aimed at exploring the therapeutic potential of targeting ferroptosis in a polyethylene-wear-debris-induced osteolysis model. Methods: Inverted cell culture model was used for stimulating the cells with wear debris in vitro, and calvarial osteolysis model was used for evaluating the therapeutic effects of inhibitors in vivo. Results: The immunostaining of periprosthetic bone tissues demonstrated a number of osteocytes expressing ferroptosis markers. Likewise, the expressions of ferroptosis markers were confirmed in polyethylene-wear-debris-stimulated osteocyte-like cells and primary osteoblasts in a direct stimulation model but not in an indirect stimulation model. Furthermore, polyethylene wear debris was implanted onto calvarial bone and mice were treated with the ferroptosis inhibitors DFO and Fer-1. These treatments alleviated the inflammatory and pathological bone resorption induced by the wear debris implantation. Conclusions: Our data broaden the knowledge of the pathogenesis of periprosthetic osteolysis and highlight ferroptosis as a promising therapeutic target.
• Visceral Fat and Ossification of the Posterior Longitudinal Ligament: Insights From a Japanese Cohort.
  Tomoya Sato; Tsutomu Endo; Yoshinao Koike; Hideki Sudo; M Alaa Terkawi; Huohuo Xue; Ryo Fujita; Soya Miura; Ryota Suzuki; Yukitoshi Shimamura; Masahiro Kanayama; Ken Kadoya; Katsuhisa Yamada; Daisuke Ukeba; Misaki Ishii; Norimasa Iwasaki
  JB & JS open access, 10, 4, 2025, [International Magazine]
  English, Scientific journal, BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) is relatively common in East Asian populations, with a recently revealed link to obesity. However, evidence linking OPLL with visceral fat obesity, which is prevalent in the Asian population, is insufficient. We aimed to examine the association between visceral fat obesity and the development of OPLL. METHODS: In a single-center case-control study, data were collected from 120 Japanese patients diagnosed with OPLL and 91 controls without spinal ligament ossification identified during health screenings. From 2020 to 2023, all participants underwent computed tomography to assess visceral fat content and spinal ligament ossification. OPLL was classified as localized (cervical spine) or diffuse (thoracic/lumbar spine). Multivariable logistic regression was conducted to assess the effect size (odds ratio [OR]) of body mass index on the incidence of OPLL and to compare outcomes between groups with a high and low visceral/subcutaneous fat area (V/S) ratio. RESULTS: The proportion of patients with visceral fat obesity was significantly higher in both the localized and diffuse OPLL groups than in the controls (58.9% vs. 64.1% vs. 25.2%, p < 0.05). Patients with OPLL had a higher rate of comorbid visceral fat obesity than the propensity score-matched controls did (56.8% vs. 18.1%, p < 0.001). The effect of BMI on the development of diffuse OPLL was 2.6-fold greater in the high V/S ratio group (OR, 9.50; 95% confidence interval [CI], 2.11 to 42.71) than in the low V/S ratio group (OR, 3.56; 95% CI, 1.51-8.37). CONCLUSIONS: Visceral fat obesity was associated with the development of OPLL, particularly diffuse OPLL. The modifying effect of visceral fat accumulation with overweight status was more strongly associated with diffuse OPLL than was that of subcutaneous fat combined with an overweight status. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
• GFRα1 Promotes Axon Regeneration after Peripheral Nerve Injury by Functioning as a Ligand.
  Tomoaki Suzuki; Ken Kadoya; Takeshi Endo; Miwako Yamasaki; Masahiko Watanabe; Norimasa Iwasaki
  Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, 4, e2400812, Jan. 2025, [International Magazine]
  English, Scientific journal, The neurotrophic factor, Glial cell line derived neurotrophi factor (GDNF), exerts a variety of biological effects through binding to its receptors, GDNF family receptor alpha-1 (GFRα1), and RET. However, the existence of cells expressing GFRα1 but not RET raises the possibility that GFRα1 can function independently from RET. Here, it is shown that GFRα1 released from repair Schwann cells (RSCs) functions as a ligand in a GDNF-RET-independent manner to promote axon regeneration after peripheral nerve injury (PNI). Local administration of GFRα1 into injured nerve promoted axon regeneration, even more when combined with GDNF blockade. GFRα1 bound to a receptor complex consisting of NCAM and integrin α7β1 of dorsal root ganglion neurons in a GDNF-RET independent manner. This is further confirmed by the Ret Y1062F knock-in mice, which cannot transmit most of GDNF-RET signaling. Finally, local administration of GFRα1 into injured sciatic nerve promoted functional recovery. These findings reveal a novel role of GFRα1 as a ligand, the molecular mechanism supporting axon regeneration by RSCs, and a novel therapy for peripheral nerve repair.
• Visceral fat obesity predicts ossification of the posterior longitudinal ligament: annual health examination data-based evidence
  Soya Miura; Yoshinao Koike; Tsutomu Endo; Masahiko Takahata; Hideki Sudo; Ken Kadoya; Masahiro Kanayama; Ryo Fujita; Shotaro Fukada; M Alaa Terkawi; Katsuhisa Yamada; Takashi Ohnishi; Daisuke Ukeba; Hiroyuki Tachi; Yuichi Hasegawa; Misaki Ishii; Norimasa Iwasaki
  The Spine Journal, Elsevier BV, Jan. 2025
  Scientific journal
• Cellular communication network factor 3 contributes to the pathological process of rheumatoid arthritis through promoting cell senescence and osteoclastogenesis in the joint.
  Taiki Tokuhiro; Gen Matsumae; Tsutomu Endo; Yuki Ogawa; Takuya Ogawa; Chen Liyile; Yoshio Nishida; Hend Alhasan; Hideyuki Kobayashi; Taku Ebata; Tomohiro Shimizu; Daisuke Takahashi; Tomohiro Onodera; Ken Kadoya; M Alaa Terkawi; Norimasa Iwasaki
  Journal of autoimmunity, 149, 103334, 103334, Dec. 2024, [International Magazine]
  English, Scientific journal, Rheumatoid arthritis (RA) is a chronic systemic and autoimmune disease that primarily affects joints and causes pain, stiffness and swelling. The affected joints exhibit severe inflammation in the synovium and bone erosion, leading to joint deformity. Aging is an important factor facilitating the development of RA, as it is associated with an increase in the number of senescent cells and the production of the autoantibodies and proinflammatory cytokines in tissues. Given that CCN3 is highly expressed in RA joints and that its level is associated with the severity of the disease, we explored its molecular function in joints and therapeutic potential in RA. An analysis of public scRNA-seq data from the RA synovium revealed that CCN3 is expressed by an inflammatory fibroblast subset. Interestingly, stimulation with CCN3 resulted in the activation of the senescence pathway in synoviocytes and osteoclast differentiation in monocytes in vitro. Consistent with these results, the administration of CCN3 into the knee joint and onto the calvarial bone resulted in increased numbers of senescent synoviocytes in the joint and osteoclasts in the bone, respectively. Furthermore, the therapeutic potential of targeting CCN3 was evaluated in an experimental RA model. Administration of the CCN3 antibody significantly suppressed inflammation and osteoclast numbers in the joints of the RA model mice. Our findings suggest that CCN3 contributes to pathological processes in RA and represents a promising therapeutic target for the treatment of RA.
• Chondroprotective functions of neutrophil-derived extracellular vesicles by promoting the production of secreted frizzled-related protein 5 in cartilage.
  Keita Kitahara; Taku Ebata; Chen Liyile; Yoshio Nishida; Yuki Ogawa; Taiki Tokuhiro; Junki Shiota; Tatsuya Nagano; Taichi E Takasuka; Tsutomu Endo; Tomohiro Shimizu; Hend Alhasan; Tsuyoshi Asano; Daisuke Takahashi; Kentaro Homan; Tomohiro Onodera; Ken Kadoya; M Alaa Terkawi; Norimasa Iwasaki
  Cell communication and signaling : CCS, 22, 1, 569, 569, 27 Nov. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND: Osteoarthritis (OA) is the most common degenerative joint disease characterized by cartilage degradation and various degrees of inflammation in the synovium. Growing evidence highlights that neutrophil extracellular vesicles (EVs) play a protective role in arthritic joints by promoting the resolution of inflammation and the synthesis of proteoglycans in cartilage. However, this homeostatic function is dependent on the activation state of neutrophils and the surrounding environment/tissues. Hence, we explored the chondroprotective functions of neutrophil-derived EVs under different stimulation conditions and the underlying molecular mechanism. METHODS: Human blood-derived neutrophils, murine bone marrow-derived neutrophils, C-28I2 cells and primary chondrocytes were used. Neutrophils were stimulated with different cytokines, and their EVs were isolated for chondrocyte stimulation and further subjected to RNA-sequencing analysis. Two experimental murine OA models were used, and the treatment was performed by intraarticular injections. RESULTS: Conditioned medium from neutrophils stimulated with TGF-β (N-β) had the greatest inhibitory effect on the expression of catabolic factors in stimulated chondrocytes. These protective effects were not impaired when conditioned medium of N-β from AnxA1-deficient mice was used. Consistent with these results, EVs isolated from N-β significantly reduced the expression of catabolic factors in stimulated chondrocytes. Bulk RNA-seq analysis revealed that secreted frizzled-related protein 5 (SFRP5) is upregulated in N-β-EV-stimulated chondrocytes. Furthermore, recombinant SFRP5 treatment significantly reduced the expression of catabolic factors in vitro and catabolic process in experimental murine OA models. CONCLUSIONS: The current study emphasizes the potential therapeutic application of neutrophils in OA and provides new knowledge on the molecular mechanisms underlying their function.
• Associations between glycan signature alterations and the cellular antigenic properties of passaged chondrocytes
  Kentaro Homan; Taiki Tokuhiro; Tomohiro Onodera; Hisatoshi Hanamatsu; Jun-ichi Furukawa; Taku Ebata; Masatake Matsuoka; Ken Kadoya; M. Alaa Terkawi; Norimasa Iwasaki
  Frontiers in Immunology, 15, Frontiers Media SA, 25 Nov. 2024
  Scientific journal, Background
  
  Cartilage repair is a significant clinical challenge because of the limited intrinsic healing capacity. Current therapeutic strategies, such as cell transplantation therapy, aim to overcome this challenge by replacing damaged tissue with healthy cells. However, the long-term survival and functionality of transplanted cells remain major hurdles.
  
  Objective
  
  This study investigated the impact of chondrocyte passaging on glycan profiles and their antigenic properties. We hypothesized that alterations in glycan composition due to passaging may contribute to the enhanced ability to activate macrophages, thereby affecting the outcome of cell transplantation therapy.
  
  Methods
  
  Peritoneal macrophages and primary articular chondrocytes were isolated from C57BL/6 mice to establish direct and indirect coculture models. Macrophage activation was assessed by measuring the concentrations of IL-6 and nitric oxide in the culture supernatants or their gene expression. Glycome analysis of various glycoconjugates was performed by glycoblotting methods combined with the SALSA procedure for N-glycans and GSLs and the BEP method for O-glycans.
  
  Results
  
  Our results revealed that direct coculture of macrophages with passaged chondrocytes increased the production of proinflammatory cytokines, including IL-6 and NO, as the number of passages increased. With increasing passage number, the expression of GD3 substantially decreased, and the expression of GM3, especially GD1a, significantly increased. Coculturing passaged GM3S knockout chondrocytes with macrophages significantly suppressed IL-6 expression, implying reduced macrophage activation.
  
  Conclusion
  
  The observed activation of macrophages due to alterations in the glycan profile of chondrocytes provides a possible explanation for the antigenicity and immune rejection of transplanted cells.
• Dynamic transcriptome analysis of osteal macrophages identifies distinct subset with senescence features in experimental osteoporosis.
  Yoshio Nishida; M Alaa Terkawi; Gen Matsumae; Shunichi Yokota; Taiki Tokuhiro; Yuki Ogawa; Hotaka Ishizu; Junki Shiota; Tsutomu Endo; Hend Alhasan; Taku Ebata; Keita Kitahara; Tomohiro Shimizu; Daisuke Takahashi; Masahiko Takahata; Ken Kadoya; Norimasa Iwasaki
  JCI insight, 31 Oct. 2024, [International Magazine]
  English, Scientific journal, Given the potential fundamental function of osteal macrophages in bone pathophysiology, we study here their precise function in experimental osteoporosis. Gene profiling of osteal macrophages from ovariectomized mice demonstrated the upregulation of genes that were involved in oxidative stress, cell senescence and apoptotic process. A scRNA-seq analysis revealed that osteal macrophages were heterogenously clustered into 6 subsets that expressed proliferative, inflammatory, anti-inflammatory and efferocytosis gene signatures. Importantly, postmenopausal mice exhibited a 20-fold increase in subset-3 that showed a typical gene signature of cell senescence and inflammation. These findings suggest that the decreased production of estrogen due to postmenopause altered the osteal macrophages subsets, resulting in a shift toward cell senescence and inflammatory conditions in the bone microenvironment. Furthermore, adoptive macrophage transfer onto calvarial bone was performed and mice that received oxidative-stressed macrophages exhibited greater osteolytic lesions than control macrophages, suggesting the role of these cells in development of inflammaging in bone microenvironment. Consistently, depletion of senescent cells and oxidative-stressed macrophages subset alleviated the excessive bone loss in postmenopausal mice. Our data provided a new insight into the pathogenesis of osteoporosis and sheds light on a new therapeutic approach for the treatment/prevention of postmenopausal osteoporosis.
• CT myelography by intrathecal injection of contrast medium though percutaneous administration route visualizes compressed cervical spinal cord in a mouse.
  Yuki Suzuki; Ken Kadoya; Akihito Sotome; Atsushi Sakuraba; Takeshi Endo; Norimasa Iwasaki
  Journal of neuroscience methods, 409, 110224, 110224, Sep. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND: Chronic compressive myelopathy (CCM) is a major cause of spinal cord disorders in the elderly, in which the spinal cord is compressed by bony or soft tissue structures. Although computed tomography myelography (CTM) has been clinically used for the diagnosis of CCM, a method of CTM in rodents remains to be developed. NEW METHOD: A 50 μl Hamilton syringe attached to a disposable needle was percutaneously inserted into the subarachnoid space (cisterna magna) between the occipital bone and C1 lamina in an anesthetized adult mouse, followed by the injection of contrast medium and CT imaging. RESULTS: CTM clearly visualized the shape of the spinal cord of intact mice and tiptoe-walking Yoshimura (Twy) mice without any health issues. COMPARISON WITH EXISTING METHOD(S): Unlike histology, the current method functions in live mice, directly depicts the compressed spinal cord, and provides clinically related image information. Furthermore, the intrathecal administration of contrast medium through the percutaneous route makes CTM less invasive and takes less time than a conventional intrathecal injection method. CONCLUSIONS: The CTM method used in the present study enables clear visualization of the shape of the dural sac and spinal cord and is useful when conducting experiments on CCM and other spinal diseases in rodents.
• 好中球由来細胞外小胞は,secreted frizzled related protein 5により軟骨変性を抑制する
  北原 圭太; 照川 アラー; 江畑 拓; 清水 智弘; 遠藤 努; 浅野 毅; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 98, 8, S1936, S1936, (公社)日本整形外科学会, Sep. 2024
  Japanese
• 整形外科領域のAI研究・開発の実際 歩行撮影とAIを使用した新規診断方法の開発 変形性膝関節症への応用
  角家 健; 宝満 健太郎; 三宅 賢稔; 浮城 健吾; 福井 大輔; 中川 弘充; 田中 毅; 大越 康充; 岩崎 倫政
  日本整形外科学会雑誌, 98, 8, S1717, S1717, (公社)日本整形外科学会, Sep. 2024
  Japanese
• 継代培養に伴う糖鎖抗原の変化と自家細胞における免疫応答の発現
  宝満 健太郎; 徳廣 泰貴; 小野寺 智洋; 花松 久寿; 古川 潤一; 江畑 拓; Terkawi Alaa; 松岡 正剛; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 98, 8, S1844, S1844, (公社)日本整形外科学会, Sep. 2024
  Japanese
• 歩行撮影とAIを使用した新規補助診断方法の開発 腰部脊柱管狭窄症での検討
  角家 健; 宝満 健太郎; 三宅 賢稔; 中川 弘充; 田中 毅; 堀脇 一樹; 大越 康充; 松野 丈夫; 武田 直樹; 須田 浩太; 岩崎 倫政
  日本整形外科学会雑誌, 98, 8, S1953, S1953, (公社)日本整形外科学会, Sep. 2024
  Japanese
• Ossification of the posterior longitudinal ligament is linked to heterotopic ossification of the ankle/foot tendons.
  Tsutomu Endo; Masahiko Takahata; Yoshinao Koike; Ryo Fujita; Daisuke Yoneoka; Masahiro Kanayama; Ken Kadoya; Tomoka Hasegawa; Mohamad Alaa Terkawi; Katsuhisa Yamada; Hideki Sudo; Taku Ebata; Misaki Ishii; Norimasa Iwasaki
  Journal of bone and mineral metabolism, 08 Jun. 2024, [Domestic magazines]
  English, Scientific journal, INTRODUCTION: Systemic osteogenesis has been speculated to be involved in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL). Our purpose was to compare the radiologic prevalence and severity of heterotopic ossification in foot tendons of Japanese patients with OPLL and to determine their association with systemic heterotopic ossification. MATERIALS AND METHODS: Clinical and radiographic data of 114 patients with OPLL were collected from 2020 to 2022. Control data were extracted from a medical database of 362 patients with ankle radiographs. Achilles and plantar tendon ossification were classified as grades 0-4, and the presence of osteophytes at five sites in the foot/ankle joint was assessed by radiography. Factors associated with the presence and severity of each ossification were evaluated by multivariable logistic regression and linear regression analysis. RESULTS: The prevalence of Achilles and plantar tendon ossification (grade ≥ 2) was 4.0-5.5 times higher in patients with OPLL (40-56%) than in the controls (10-11%). The presence of Achilles tendon ossification was associated with OPLL, age, and coexisting plantar tendon ossification, and was most strongly associated with OPLL (standardized regression coefficient, 0.79; 95% confidence interval, 1.34-2.38). The severity of Achilles and plantar tendon ossification was associated with the severity of ossification of the entire spinal ligament. CONCLUSIONS: The strong association of foot tendon ossification with OPLL suggests that patients with OPLL have a systemic osteogenesis background. These findings will provide a basis for exploring new treatment strategies for OPLL, including control of metabolic abnormalities.
• 炎症収束型好中球由来細胞外小胞は、secreted frizzled related protein 5により軟骨変性を抑制する
  北原 圭太; 江畑 拓; 西田 善郎; 塩田 惇喜; 徳廣 泰貴; 小川 裕生; 小川 拓也; 清水 智弘; 遠藤 努; 浅野 毅; 高橋 大介; 角家 健; 照川 アラー; 岩崎 倫政
  北海道整形災害外科学会雑誌, 66, 143rd suppl, 23, 23, 北海道整形災害外科学会, 2024
  Japanese
• 歩行撮影とAIを使用した新規補助診断方法の開発 腰部脊柱管狭窄症での検討 Gait based prediction of lumbar spinal stenosis using artificial intelligence
  角家 健; 宝満 健太郎; 三宅 賢稔; 岩崎 倫政; 中川 弘充; 田中 毅; 堀脇 一樹; 大越 康充; 松野 丈夫; 武田 直樹; 須田 浩太
  北海道整形災害外科学会雑誌, 66, 143rd suppl, 43, 43, 北海道整形災害外科学会, 2024
  Japanese
• 継代細胞における糖鎖シグネチャーの解明
  宝満 健太郎; 徳廣 泰貴; 小野寺 智洋; 江畑 拓; Alaa Terkawi; 松岡 正剛; 花松 久寿; 古川 潤一; 角家 健; 岩崎 倫政
  北海道整形災害外科学会雑誌, 66, 143rd suppl, 85, 85, 北海道整形災害外科学会, 2024
  Japanese
• ラット坐骨神経を使用した慢性絞扼性神経障害の新規モデル開発
  山本 康弘; 角家 健; 内藤 聖人; 岩崎 倫政; 石島 旨章
  末梢神経, 34, 2, 299, 299, 日本末梢神経学会, Dec. 2023
  Japanese
• 炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用についての検討
  北原 圭太; 江畑 拓; 照川 アラー; 清水 智弘; 遠藤 努; 浅野 毅; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 97, 8, S1667, S1667, (公社)日本整形外科学会, Aug. 2023
  Japanese
• ラット坐骨神経を使用した慢性絞扼性神経障害の新規モデル開発
  山本 康弘; 角家 健; 内藤 聖人; 石島 旨章; 岩崎 倫政
  日本整形外科学会雑誌, 97, 8, S1757, S1757, (公社)日本整形外科学会, Aug. 2023
  Japanese
• 炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用についての検討
  北原 圭太; 江畑 拓; 照川 アラー; 清水 智弘; 遠藤 努; 浅野 毅; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 97, 8, S1667, S1667, (公社)日本整形外科学会, Aug. 2023
  Japanese
• High whole-body bone mineral density in ossification of the posterior longitudinal ligament.
  Ryo Fujita; Tsutomu Endo; Masahiko Takahata; Yoshinao Koike; Daisuke Yoneoka; Ryota Suzuki; Masaru Tanaka; Katsuhisa Yamada; Hideki Sudo; Tomoka Hasegawa; Mohamad Alaa Terkawi; Ken Kadoya; Norimasa Iwasaki
  The spine journal : official journal of the North American Spine Society, 23, 10, 1461, 1470, 10 Jul. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND CONTEXT: Recent studies suggest that ossification of the posterior longitudinal ligament (OPLL) is exacerbated by systemic metabolic disturbances, including obesity. However, although an increase in bone mineral density (BMD) measured at the lumbar spine has been reported in patients with OPLL, no studies have investigated the systemic BMD of patients with OPLL in detail. PURPOSE: We investigated whether patients with OPLL develop increased whole-body BMD. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with symptomatic OPLL (OPLL [+]; n=99). Control data (OPLL [-]; n=226) without spinal ligament ossification were collected from patients who underwent spinal decompression, spinal fusion, or hip replacement surgery. OUTCOME MEASURES: Demographic data, including age, body mass index (BMI), comorbidities, history of treatment for osteoporosis, and history of vertebral and nonvertebral fractures, was obtained from all participants. In addition, whole-body BMD, including the lumbar spine, thoracic spine, femoral neck, skull, ribs, entire upper extremity, entire lower extremity, and pelvis, were measured in all participants using whole-body dual-energy X-ray absorptiometry. METHODS: Patient data were collected from 2018 to 2022. All participants were categorized based on sex, age (middle-aged [<70 years] and older adults [≥70 years]), and OPLL type (localized OPLL [OPLL only in the cervical spine], diffuse OPLL [OPLL in regions including the thoracic spine]), and OPLL [-]) and each parameter was compared. The factors associated with whole-body BMD were evaluated via multivariable linear regression analysis. RESULTS: Compared with the OPLL (-) group, the OPLL (+) group of older women had significantly higher BMD in all body parts (p<.01), and the OPLL (+) group of older men had significantly higher BMD in all body parts except the ribs, forearm, and skull (p<.01). The factors associated with increased BMD of both the femoral neck (load-bearing bone) and skull (nonload-bearing bone) were age, BMI, and coexisting diffuse OPLL in women and BMI and coexisting localized OPLL in men. CONCLUSIONS: Patients with OPLL have increased whole-body BMD regardless of sex, indicating that it is not simply due to load-bearing from obesity. These findings suggested that OPLL is associated with a systemic pathology.
• Dyslipidemia as a novel risk for the development of symptomatic ossification of the posterior longitudinal ligament.
  Shotaro Fukada; Tsutomu Endo; Masahiko Takahata; Masahiro Kanayama; Yoshinao Koike; Ryo Fujita; Ryota Suzuki; Toshifumi Murakami; Tomoka Hasegawa; Mohamad Alaa Terkawi; Tomoyuki Hashimoto; Kastuhisa Yamada; Hideki Sudo; Ken Kadoya; Norimasa Iwasaki
  The spine journal : official journal of the North American Spine Society, 23, 9, 1287, 1295, 07 May 2023, [International Magazine]
  English, Scientific journal, BACKGROUND CONTEXT: Obesity and visceral fat have been implicated as potential factors in the pathogenesis of the ossification of the posterior longitudinal ligament (OPLL); the details of the factors involved in OPLL remain unclear. PURPOSE: We aimed to determine the association between dyslipidemia and symptomatic OPLL. STUDY DESIGN: Single institution cross-sectional study. PATIENT SAMPLE: Data were collected from Japanese patients with OPLL (n=92) who underwent whole-spine computed tomography scanning. Control data (n=246) without any spinal ligament ossification were collected from 627 Japanese participants who underwent physical examination. OUTCOME MEASURES: Baseline information and lipid parameters, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) from fasting blood samples were collected to assess the comorbidity of dyslipidemia. METHODS: Patient data were collected from 2020 to 2022. Patients with dyslipidemia were defined as those who were taking medication for dyslipidemia and who met one of the following criteria: TG ≥150 mg/dL, LDL-C ≥140 mg/dL, and/or HDL-C <40 mg/dL. The factors associated with OPLL development were evaluated using multivariate logistic regression analysis. RESULTS: The comorbidity of dyslipidemia in the OPLL group was more than twice that in the control group (71.7% and 35.4%, respectively). The mean body mass index (BMI) of the OPLL group was significantly higher than that of the control group (27.2 kg/m2 and 23.0 kg/m2). Multivariate logistic regression analysis revealed that dyslipidemia was associated with the development of OPLL (regression coefficient, 0.80; 95% confidence interval, 0.11-1.50). Additional risk factors included age, BMI, and diabetes mellitus. CONCLUSIONS: We demonstrated a novel association between dyslipidemia and symptomatic OPLL development using serum data. This suggests that visceral fat obesity or abnormal lipid metabolism are associated with the mechanisms of onset and exacerbation of OPLL as well as focal mechanical irritation due to being overweight.
• Peripheral nerve-derived fibroblasts promote neurite outgrowth in adult dorsal root ganglion neurons more effectively than skin-derived fibroblasts.
  Masato Hara; Ken Kadoya; Takeshi Endo; Norimasa Iwasaki
  Experimental physiology, 108, 4, 621, 635, Apr. 2023, [International Magazine]
  English, Scientific journal, NEW FINDINGS: What is the central question of this study? Although fibroblasts are involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. What is the main finding and its importance? Nerve-derived fibroblasts have a greater neurite-promoting effect than skin-derived fibroblasts, and epineurium-derived fibroblasts can promote neurite outgrowth more effectively than parenchyma-derived fibroblasts. The epineurium-derived fibroblasts and parenchyma-derived fibroblasts have distinctly different molecular profiles, including genes of soluble factors to promote axonal growth. Fibroblasts are molecularly and functionally different depending on their localization in nerve tissue, and epineurium-derived fibroblasts might be involved in axon regeneration after peripheral nerve injury more than previously thought. ABSTRACT: Although fibroblasts (Fb) are components of a peripheral nerve involved in the regenerative process associated with peripheral nerve injury, detailed information regarding their characteristics is largely lacking. The objective of the present study was to investigate the capacity of Fb derived from peripheral nerves to stimulate the outgrowth of neurites from adult dorsal root ganglion neurons and to clarify their molecular characteristics. Fibroblasts were prepared from the epineurium and parenchyma of rat sciatic nerves and skin. The Fb derived from epineurium showed the greatest effect on neurite outgrowth, followed by the Fb derived from parenchyma, indicating that Fb derived from nerves promote neurite outgrowth more effectively than skin-derived Fb. Although both soluble and cell-surface factors contributed evenly to the neurite-promoting effect of nerve-derived Fb, in crush and transection injury models, Fb were not closely associated with regenerating axons, indicating that only soluble factors from Fb are available to regenerating axons. A transcriptome analysis revealed that the molecular profiles of these Fb were distinctly different and that the gene expression profiles of soluble factors that promote axonal growth are unique to each Fb. These findings indicate that Fb are molecularly and functionally different depending on their localization in nerve tissue and that Fb derived from epineurium might be involved more than was previously thought in axon regeneration after peripheral nerve injury.
• Macrophage‐derived extracellular vesicles trigger non‐canonical pyroptosis in chondrocytes leading to cartilage catabolism in osteoarthritis
  Taku Ebata; Mohamad Alaa Terkawi; Keita Kitahara; Syunichi Yokota; Junki Shiota; Yoshio Nishida; Gen Matsumae; Hend Alhasan; Masanari Hamasaki; Kazutoshi Hontani; Tomohiro Shimizu; Daisuke Takahashi; Tsutomu Endo; Tomohiro Onodera; Ken Kadoya; Norimasa Iwasaki
  Arthritis & Rheumatology, 16 Mar. 2023, [International Magazine]
  English, Scientific journal, OBJECTIVES: The severity of osteoarthritis and cartilage degeneration are highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. Here, we explored the pathological role of inflammatory macrophage extracellular vesicles in cartilage degeneration. METHODS: Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages and the resulting extracellular vesicles were harvested for chondrocyte stimulation in vitro and intraarticular injection in a mouse model. The stimulated chondrocytes were further subjected to RNA-seq analysis and other functional assays. The action of caspase-11 was disrupted in vitro using a specific siRNA or wedelolactone, and in experimental OA-murine models by the intraarticular injection of wedelolactone. RESULTS: Stimulated chondrocytes exhibited a significant elevation in the expression of chondrocyte catabolic factors. Consistent with these results, RNA-seq analyses of stimulated chondrocytes indicated that upregulated genes are mainly categorized into apoptotic process and TNF-signaling pathway which suggests the induction of apoptotic process. Moreover, these chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase-11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and the pathological changes in collagenase-and joint instability-induced OA models. CONCLUSIONS: Our results provide a new insight into the pathological mechanisms of OA and suggest that non-canonical pyroptosis in chondrocytes represents an attractive therapeutic target for future treatment.
• 人工関節置換術後無菌性緩みの局所骨溶解におけるチミジンホスホリラーゼの機能解析
  松前 元; 清水 智弘; 田 園; 高橋 大介; 江畑 拓; 照川 ヘンド; 横田 隼一; 角家 健; 照川 アラー; 岩崎 倫政
  北海道整形災害外科学会雑誌, 64, 2, 59, 72, 北海道整形災害外科学会, Mar. 2023
  Japanese
• 末梢神経再生治療の最前線-基礎から臨床へ- シュワン細胞の軸索再生メカニズムから考える末梢神経再生治療戦略
  遠藤 健; 角家 健; 鈴木 智亮; 鈴木 裕貴; 照川 アラー; 河村 太介; 岩崎 倫政
  日本整形外科学会雑誌, 97, 2, S154, S154, (公社)日本整形外科学会, Mar. 2023
  Japanese
• 慢性絞扼性神経障害の新規動物モデル開発と病態解明
  山本 康弘; 角家 健; 内藤 聖人; 石島 旨章; 岩崎 倫政
  日本整形外科学会雑誌, 97, 2, S316, S316, (公社)日本整形外科学会, Mar. 2023
  Japanese
• 人工関節置換術後無菌性緩みの局所骨溶解におけるチミジンホスホリラーゼの機能解析
  松前 元; 清水 智弘; 田 園; 高橋 大介; 江畑 拓; 照川 ヘンド; 横田 隼一; 角家 健; 照川 アラー; 岩崎 倫政
  北海道整形災害外科学会雑誌, 64, 2, 59, 72, 北海道整形災害外科学会, Mar. 2023
  Japanese
• Lumbar ossification of the ligamentum flavum reflects a strong ossification tendency of the entire spinal ligament.
  Kazuha Nakabachi; Tsutomu Endo; Masahiko Takahata; Ryo Fujita; Yoshinao Koike; Ryota Suzuki; Yuichi Hasegawa; Toshifumi Murakami; Katsuhisa Yamada; Hideki Sudo; Mohamad Alaa Terkawi; Ken Kadoya; Norimasa Iwasaki
  Scientific reports, 13, 1, 638, 638, 12 Jan. 2023, [International Magazine]
  English, Scientific journal, Patients with ossification of the ligamentum flavum (OLF) in the lumbar spine may be at high risk of developing concomitant ossification of the entire spinal ligament, but the etiology remains unclear. We investigated the propensity for spinal ligament ossification in asymptomatic subjects with lumbar OLF using the data of 595 Japanese individuals receiving medical check-ups, including computed tomography (CT) scanning. The severity of OLF (total number of intervertebral segments with OLF) of the entire spine on CT was quantified using an OLF index. Subjects with OLF were grouped according to this index: localized OLF (n = 138), intermediate OLF (n = 70), and extensive OLF (n = 31). The proportion of subjects with lumbar OLF increased with increasing OLF index (localized 13.7%, intermediate 41.4%, and extensive 70.9%). Multiple regression analysis found that lumbar OLF index was associated with thoracic OLF index, and co-existence of ossification of the posterior longitudinal ligament (OPLL) of the thoracic and lumbar spine. This study showed that subjects with more multilevel lumbar OLF were more likely to develop multilevel thoracic OLF and to have coexisting OPLL. Patients with lumbar OLF may be a distinctive subgroup with a strong tendency to ossification of the entire spinal ligament.
• 炎症収束型好中球由来細胞外小胞による軟骨細胞における抗異化作用の検討
  北原 圭太; 江畑 拓; 横田 隼一; 塩田 惇喜; 西田 善郎; 徳廣 泰貴; 清水 智弘; 浅野 毅; 高橋 大介; 角家 健; 岩崎 倫政
  北海道整形災害外科学会雑誌, 65, 142nd suppl, 66, 66, 北海道整形災害外科学会, 2023
  Japanese
• Spinal Canal and Spinal Cord in Rat Continue to Grow Even after Sexual Maturation: Anatomical Study and Molecular Proposition.
  Akihito Sotome; Ken Kadoya; Yuki Suzuki; Norimasa Iwasaki
  International journal of molecular sciences, 23, 24, 16 Dec. 2022, [International Magazine]
  English, Scientific journal, Although rodents have been widely used for experimental models of spinal cord diseases, the details of the growth curves of their spinal canal and spinal cord, as well as the molecular mechanism of the growth of adult rat spinal cords remain unavailable. They are particularly important when conducting the experiments of cervical spondylotic myelopathy (CSM), since the disease condition depends on the size of the spinal canal and the spinal cord. Thus, the purposes of the present study were to obtain accurate growth curves for the spinal canal and spinal cord in rats; to define the appropriate age in weeks for their use as a CSM model; and to propose a molecular mechanism of the growth of the adult spinal cord in rats. CT myelography was performed on Lewis rats from 4 weeks to 40 weeks of age. The vertical growth of the spinal canal at C5 reached a plateau after 20 and 12 weeks, and at T8 after 20 and 16 weeks, in males and females, respectively. The vertical growth of the C5 and T8 spinal cord reached a plateau after 24 weeks in both sexes. The vertical space available for the cord (SAC) of C5 and T8 did not significantly change after 8 weeks in either sex. Western blot analyses showed that VEGFA, FGF2, and BDNF were highly expressed in the cervical spinal cords of 4-week-old rats, and that the expression of these growth factors declined as rats grew. These findings indicate that the spinal canal and the spinal cord in rats continue to grow even after sexual maturation and that rats need to be at least 8 weeks of age for use in experimental models of CSM. The present study, in conjunction with recent evidence, proposes the hypothetical model that the growth of rat spinal cord after the postnatal period is mediated at least in part by differentiation of neural progenitor cells and that their differentiation potency is maintained by VEGFA, FGF2, and BDNF.
• 好中球細胞外トラップによる末梢神経ワーラー変性の修復阻害
  山本 康弘; 角家 健; 市原 理司; 原 章; 照川 アラー; 石島 旨章; 岩崎 倫政
  末梢神経, 33, 2, 245, 245, 日本末梢神経学会, Dec. 2022
  Japanese
• Molecular and Regenerative Characterization of Repair and Non-repair Schwann Cells.
  Tomoaki Suzuki; Ken Kadoya; Takeshi Endo; Norimasa Iwasaki
  Cellular and molecular neurobiology, 12 Oct. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Although evidence has accumulated to indicate that Schwann cells (SCs) differentiate into repair SCs (RSCs) upon injury and that the unique phenotype of these cells allow them to provide support for peripheral nerve regeneration, the details of the RSCs are not fully understood. The findings of the current study indicate that the RSCs have enhanced adherent properties and a greater capability to promote neurite outgrowth and axon regeneration after peripheral nerve injury, compared to the non-RSCs. Further, transcriptome analyses have demonstrated that the molecular signature of the RSCs is distinctly different from that of the non-RSCs. The RSCs upregulate a group of genes that are related to inflammation, repair, and regeneration, whereas non-RSCs upregulate genes related to myelin maintenance, Notch, and aging. These findings indicate that the RSCs have markedly different cellular, regenerative, and molecular characteristics compared to the non-RSCs, even though the RSCs were just derived from non-RSCs upon injury, thus providing the basis for understanding the mechanisms related to SC mediated repair after peripheral nerve injury.
• Neutrophils delay repair process in Wallerian degeneration by releasing NETs outside the parenchyma.
  Yasuhiro Yamamoto; Ken Kadoya; Mohamad Alaa Terkawi; Takeshi Endo; Kohtarou Konno; Masahiko Watanabe; Satoshi Ichihara; Akira Hara; Kazuo Kaneko; Norimasa Iwasaki; Muneaki Ishijima
  Life science alliance, 5, 10, Oct. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Although inflammation is indispensable for the repair process in Wallerian degeneration (WD), the role of neutrophils in the WD repair process remains unclear. After peripheral nerve injury, neutrophils accumulate at the epineurium but not the parenchyma in the WD region because of the blood-nerve barrier. An increase or decrease in the number of neutrophils delayed or promoted macrophage infiltration from the epineurium into the parenchyma and the repair process in WD. Abundant neutrophil extracellular traps (NETs) were formed around neutrophils, and its inhibition dramatically increased macrophage infiltration into the parenchyma. Furthermore, inhibition of either MIF or its receptor, CXCR4, in neutrophils decreased NET formation, resulting in enhanced macrophage infiltration into the parenchyma. Moreover, inhibiting MIF for just 2 h after peripheral nerve injury promoted the repair process. These findings indicate that neutrophils delay the repair process in WD from outside the parenchyma by inhibiting macrophage infiltration via NET formation and that neutrophils, NETs, MIF, and CXCR4 are therapeutic targets for peripheral nerve regeneration.
• High-Throughput Screening Assay Identifies Berberine and Mubritinib as Neuroprotection Drugs for Spinal Cord Injury via Blood-Spinal Cord Barrier Protection.
  Yuki Suzuki; Shinsuke Nakagawa; Takeshi Endo; Akihito Sotome; Rufei Yuan; Tsuyoshi Asano; Satoko Otsuguro; Katsumi Maenaka; Norimasa Iwasaki; Ken Kadoya
  Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics, 19, 6, 1976, 1991, 30 Sep. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Because the breakdown of the blood-brain spinal cord barrier (BBSCB) worsens many central nervous system (CNS) diseases, prevention of BBSCB breakdown has been a major therapeutic target, especially for spinal cord injury (SCI). However, effective drugs that protect BBSCB function have yet to be developed. The purpose of the current study was 1) to develop a high-throughput screening assay (HTSA) to identify candidate drugs to protect BBSCB function, 2) to identify candidate drugs from existing drugs with newly developed HTSA, and 3) to examine the therapeutic effects of candidate drugs on SCI. Our HTSA included a culture of immortalized human brain endothelial cells primed with candidate drugs, stress with H2O2, and evaluation of their viability. A combination of the resazurin-based assay with 0.45 mM H2O2 qualified as a reliable HTSA. Screening of 1,570 existing drugs identified 90 drugs as hit drugs. Through a combination of reproducibility tests, exclusion of drugs inappropriate for clinical translation, and dose dependency tests, berberine, mubritinib, and pioglitazone were identified as a candidate. An in vitro BBSCB functional test revealed that berberine and mubritinib, but not pioglitazone, protected BBSCB from oxygen-glucose deprivation and reoxygenation stress. Additionally, these two drugs minimized BBSCB breakdown 1 day after cervical SCI in mice. Furthermore, berberine and mubritinib reduced neuronal loss and improved gait performance 8 weeks after SCI. Collectively, the current study established a useful HTSA to identify potential neuroprotective drugs by maintaining BBSCB function and demonstrated the neuroprotective effect of berberine and mubritinib after SCI.
• 骨粗鬆症における骨マクロファージのサブタイプ変化とその機能解析
  松前 元; 照川 アラー; 横田 隼一; 江畑 拓; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 96, 8, S1536, S1536, (公社)日本整形外科学会, Sep. 2022
  Japanese
• ウェアラブルデバイスの有用性 足部ウェアラブルデバイスによる歩行解析の妥当性と臨床研究の実際
  角家 健; 宝満 健太郎; 岩崎 倫政
  日本関節病学会誌, 41, 3, 209, 209, (一社)日本関節病学会, Sep. 2022
  Japanese
• 炎症収束型好中球由来細胞外小胞による軟骨細胞抗異化作用の検討
  北原 圭太; 江畑 拓; 清水 智弘; 浅野 毅; 照川 アラー; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 96, 8, S1559, S1559, (公社)日本整形外科学会, Sep. 2022
  Japanese
• 軟骨細胞パイロトーシス制御による軟骨変性抑制効果
  江畑 拓; 照川 アラー; 横田 隼一; 照川 ヘンド; 松前 元; 清水 智弘; 高橋 大介; 小野寺 智洋; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 96, 8, S1580, S1580, (公社)日本整形外科学会, Sep. 2022
  Japanese
• 好中球細胞外トラップによる末梢神経ワーラー変性の修復阻害
  山本 康弘; 角家 健; 市原 理司; 原 章; 照川 アラー; 石島 旨章; 岩崎 倫政
  日本整形外科学会雑誌, 96, 8, S1685, S1685, (公社)日本整形外科学会, Sep. 2022
  Japanese
• Inhibitory role of Annexin A1 in pathological bone resorption and therapeutic implications in periprosthetic osteolysis.
  Hend Alhasan; Mohamad Alaa Terkawi; Gen Matsumae; Taku Ebata; Yuan Tian; Tomohiro Shimizu; Yoshio Nishida; Shunichi Yokota; Fayna Garcia-Martin; Mahmoud M Abd Elwakil; Daisuke Takahashi; Mahmoud A Younis; Hideyoshi Harashima; Ken Kadoya; Norimasa Iwasaki
  Nature communications, 13, 1, 3919, 3919, 07 Jul. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, There is currently no therapy available for periprosthetic osteolysis, the most common cause of arthroplasty failure. Here, the role of AnxA1 in periprosthetic osteolysis and potential therapeutics were investigated. Reducing the expression of AnxA1 in calvarial tissue was found to be associated with increased osteolytic lesions and the osteolytic lesions induced by debris implantation were more severe in AnxA1-defecient mice than in wild-type mice. AnxA1 inhibits the differentiation of osteoclasts through suppressing NFκB signaling and promoting the PPAR-γ pathway. Administration of N-terminal-AnxA1 (Ac2-26 peptide) onto calvariae significantly reduced osteolytic lesions triggered by wear debris. These therapeutic effects were abrogated in mice that had received the PPAR-γ antagonist, suggesting that the AnxA1/PPAR-γ axis has an inhibitory role in osteolysis. The administration of Ac2-26 suppressed osteolysis induced by TNF-α and RANKL injections in mice. These findings indicate that AnxA1 is a potential therapeutic agent for the treatment of periprosthetic osteolysis.
• Retrograde Axonal Transport of Liposomes from Peripheral Tissue to Spinal Cord and DRGs by Optimized Phospholipid and CTB Modification.
  Takafumi Fukui; Hironao Tateno; Takashi Nakamura; Yuma Yamada; Yusuke Sato; Norimasa Iwasaki; Hideyoshi Harashima; Ken Kadoya
  International journal of molecular sciences, 23, 12, 15 Jun. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Despite recent advancements in therapeutic options for disorders of the central nervous system (CNS), the lack of an efficient drug-delivery system (DDS) hampers their clinical application. We hypothesized that liposomes could be optimized for retrograde transport in axons as a DDS from peripheral tissues to the spinal cord and dorsal root ganglia (DRGs). Three types of liposomes consisting of DSPC, DSPC/POPC, or POPC in combination with cholesterol (Chol) and polyethylene glycol (PEG) lipid were administered to sciatic nerves or the tibialis anterior muscle of mature rats. Liposomes in cell bodies were detected with infrared fluorescence of DiD conjugated to liposomes. Three days later, all nerve-administered liposomes were retrogradely transported to the spinal cord and DRGs, whereas only muscle-administered liposomes consisting of DSPC reached the spinal cord and DRGs. Modification with Cholera toxin B subunit improved the transport efficiency of liposomes to the spinal cord and DRGs from 4.5% to 17.3% and from 3.9% to 14.3% via nerve administration, and from 2.6% to 4.8% and from 2.3% to 4.1% via muscle administration, respectively. Modification with octa-arginine (R8) improved the transport efficiency via nerve administration but abolished the transport capability via muscle administration. These findings provide the initial data for the development of a novel DDS targeting the spinal cord and DRGs via peripheral administration.
• 【末梢神経再生】末梢神経再生に至適なシュワン細胞の分化度の同定
  遠藤 健; 角家 健
  末梢神経, 33, 1, 36, 43, 日本末梢神経学会, Jun. 2022
  Japanese
• IL4 stimulated macrophages promote axon regeneration after peripheral nerve injury by secreting uPA to stimulate uPAR upregulated in injured axons.
  Yuki Matsui; Ken Kadoya; Yusuke Nagano; Takeshi Endo; Masato Hara; Gen Matsumae; Tomoaki Suzuki; Yasuhiro Yamamoto; Mohamad Alaa Terkawi; Norimasa Iwasaki
  Cellular and molecular life sciences : CMLS, 79, 6, 289, 289, 10 May 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Accumulating evidences suggest that M2 macrophages are involved with repair processes in the nervous system. However, whether M2 macrophages can promote axon regeneration by directly stimulating axons nor its precise molecular mechanism remains elusive. Here, the current study demonstrated that typical M2 macrophages, which were generated by IL4 simulation, had the capacity to stimulate axonal growth by their direct effect on axons and that the graft of IL4 stimulated macrophages into the region of Wallerian degeneration enhanced axon regeneration and improved functional recovery after PNI. Importantly, uPA (urokinase plasminogen activator)-uPA receptor (uPAR) was identified as the central axis underlying the axon regeneration effect of IL4 stimulated macrophages. IL4 stimulated macrophages secreted uPA, and its inhibition abolished their axon regeneration effect. Injured but not intact axons expressed uPAR to be sensitive to uPA. These results unveil a cellular and molecular mechanism underlying the macrophage related axon regeneration and provide a basis of a novel therapy for PNI.
• Low-Grade Inflammation in the Pathogenesis of Osteoarthritis: Cellular and Molecular Mechanisms and Strategies for Future Therapeutic Intervention.
  M Alaa Terkawi; Taku Ebata; Shunichi Yokota; Daisuke Takahashi; Tsutomu Endo; Gen Matsumae; Tomohiro Shimizu; Ken Kadoya; Norimasa Iwasaki
  Biomedicines, 10, 5, 10 May 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Osteoarthritis (OA) is a musculoskeletal disease characterized by cartilage degeneration and stiffness, with chronic pain in the affected joint. It has been proposed that OA progression is associated with the development of low-grade inflammation (LGI) in the joint. In support of this principle, LGI is now recognized as the major contributor to the pathogenesis of obesity, aging, and metabolic syndromes, which have been documented as among the most significant risk factors for developing OA. These discoveries have led to a new definition of the disease, and OA has recently been recognized as a low-grade inflammatory disease of the joint. Damage-associated molecular patterns (DAMPs)/alarmin molecules, the major cellular components that facilitate the interplay between cells in the cartilage and synovium, activate various molecular pathways involved in the initiation and maintenance of LGI in the joint, which, in turn, drives OA progression. A better understanding of the pathological mechanisms initiated by LGI in the joint represents a decisive step toward discovering therapeutic strategies for the treatment of OA. Recent findings and discoveries regarding the involvement of LGI mediated by DAMPs in OA pathogenesis are discussed. Modulating communication between cells in the joint to decrease inflammation represents an attractive approach for the treatment of OA.
• Comprehensive validation of a wearable foot sensor system for estimating spatiotemporal gait parameters by simultaneous three-dimensional optical motion analysis.
  Kentaro Homan; Keizo Yamamoto; Ken Kadoya; Naoki Ishida; Norimasa Iwasaki
  BMC sports science, medicine & rehabilitation, 14, 1, 71, 71, 17 Apr. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, BACKGROUND: Use of a wearable gait analysis system (WGAS) is becoming common when conducting gait analysis studies due to its versatility. At the same time, its versatility raises a concern about its accuracy, because its calculations rely on assumptions embedded in its algorithms. The purpose of the present study was to validate twenty spatiotemporal gait parameters calculated by the WGAS by comparison with simultaneous measurements taken with an optical motion capture system (OMCS). METHODS: Ten young healthy volunteers wore two inertial sensors of the commercially available WGAS, Physilog®, on their feet and 23 markers for the OMCS on the lower part of the body. The participants performed at least three sets of 10-m walk tests at their self-paced speed in the laboratory equipped with 12 high-speed digital cameras with embedded force plates. To measure repeatability, all participants returned for a second day of testing within two weeks. RESULTS: Twenty gait parameters calculated by the WGAS had a significant correlation with the ones determined by the OMCS. Bland and Altman analysis showed that the between-device agreement for twenty gait parameters was within clinically acceptable limits. The validity of the gait parameters generated by the WGAS was found to be excellent except for two parameters, swing width and maximal heel clearance. The repeatability of the WGAS was excellent when measured between sessions. CONCLUSION: The present study showed that spatiotemporal gait parameters estimated by the WGAS were reasonably accurate and repeatable in healthy young adults, providing a scientific basis for applying this system to clinical studies.
• 好中球は末梢神経ワーラー変性部の神経上膜に集積して修復機転を阻害する
  山本 康弘; 角家 健; 市原 理司; 原 章; 照川 アラー; 今野 幸太郎; 渡辺 雅彦; 金子 和夫; 石島 旨章; 岩崎 倫政
  日本整形外科学会雑誌, 96, 2, S74, S74, (公社)日本整形外科学会, Mar. 2022
  Japanese
• Interplay between Inflammation and Pathological Bone Resorption: Insights into Recent Mechanisms and Pathways in Related Diseases for Future Perspectives.
  M Alaa Terkawi; Gen Matsumae; Tomohiro Shimizu; Daisuke Takahashi; Ken Kadoya; Norimasa Iwasaki
  International journal of molecular sciences, 23, 3, 04 Feb. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Bone is a mineralized and elastic connective tissue that provides fundamental functions in the human body, including mechanical support to the muscles and joints, protection of vital organs and storage of minerals. Bone is a metabolically active organ that undergoes continuous remodeling processes to maintain its architecture, shape, and function throughout life. One of the most important medical discoveries of recent decades has been that the immune system is involved in bone remodeling. Indeed, chronic inflammation has been recognized as the most significant factor influencing bone homeostasis, causing a shift in the bone remodeling process toward pathological bone resorption. Bone osteolytic diseases typified by excessive bone resorption account for one of the greatest causes of disability worldwide, with significant economic and public health burdens. From this perspective, we discuss the recent findings and discoveries highlighting the cellular and molecular mechanisms that regulate this process in the bone microenvironment, in addition to the current therapeutic strategies for the treatment of osteolytic bone diseases.
• Mature but not developing Schwann cells promote axon regeneration after peripheral nerve injury.
  Takeshi Endo; Ken Kadoya; Tomoaki Suzuki; Yuki Suzuki; Mohamad Alaa Terkawi; Daisuke Kawamura; Norimasa Iwasaki
  NPJ Regenerative medicine, 7, 1, 12, 12, 28 Jan. 2022, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Since Schwann cells (SCs) support axonal growth at development as well as after peripheral nerve injury (PNI), developing SCs might be able to promote axon regeneration after PNI. The purpose of the current study was to elucidate the capability of developing SCs to induce axon regeneration after PNI. SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs) from injured nerves, and non-RSCs from intact nerves were tested by grafting into acellular region of rat sciatic nerve with crush injury. Both of developing SCs completely failed to support axon regeneration, whereas both of mature SCs, especially RSCs, induced axon regeneration. Further, RSCs but not SCPs promoted neurite outgrowth of adult dorsal root ganglion neurons. Transcriptome analysis revealed that the gene expression profiles were distinctly different between RSCs and SCPs. These findings indicate that developing SCs are markedly different from mature SCs in terms of functional and molecular aspects and that RSC is a viable candidate for regenerative cell therapy for PNI.
• 地域在住高齢者における歩行と認知機能の関連 横断研究(Association of gait with cognitive function among community-dwelling older adults: a cross-sectional study)
  Hao Wen; Zhao Wenjing; Kimura Takashi; Ukawa Shigekazu; Kadoya Ken; Kondo Katsunori; Tamakoshi Akiko
  Journal of Epidemiology, 32, Suppl.1, 92, 92, (一社)日本疫学会, Jan. 2022
  English
• Evaluation of biological responses to micro-particles derived from a double network hydrogel
  Gen Matsumae; Mohamad Alaa Terkawi; Takayuki Nonoyama; Takayuki Kurokawa; Daisuke Takahashi; Tomohiro Shimizu; Ken Kadoya; Jian Ping Gong; Kazunori Yasuda; Norimasa Iwasaki
  Biomaterials Science, Royal Society of Chemistry (RSC), 2022, [Peer-reviewed]
  Scientific journal, Double network hydrogels have been proven to be a substitute biomaterial for cartilage. For further applications as articular cartilages, it is essential to understand the biological reactions that might be initiated by their micro-particles.
• 末梢神経損傷後早期免疫反応の詳細 好中球由来MIFによる修復機転の阻害
  山本 康弘; 角家 健; 市原 理司; 原 章; Terkawi Alaa; 今野 幸太郎; 渡辺 雅彦; 岩崎 倫政; 金子 和夫; 石島 旨章
  末梢神経, 32, 2, 268, 268, 日本末梢神経学会, Dec. 2021
  Japanese
• Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates bone loss in osteoporosis mouse models by suppressing osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway.
  Shunichi Yokota; Gen Matsumae; Tomohiro Shimizu; Tomoka Hasegawa; Taku Ebata; Daisuke Takahashi; Cai Heguo; Yuan Tian; Hend Alhasan; Masahiko Takahata; Ken Kadoya; Mohamad Alaa Terkawi; Norimasa Iwasaki
  Bone, 153, 116140, 116140, Dec. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, A growing body of evidence suggests that immune factors that regulate osteoclast differentiation and bone resorption might be promising therapeutic agents for the treatment of osteoporosis. The expression of CLCF1, an immune cell-derived molecule, has been reported to be reduced in patients with postmenopausal osteoporosis. This suggests that it may be involved in bone remodeling. Thus, we explored the functional role of CLCF1 in osteoclastogenesis and bone loss associated with osteoporosis. Surprisingly, the administration of recombinant CLCF1 repressed excessive bone loss in ovariectomized mice and prevented RANKL-induced bone loss in calvarial mouse model. Likewise, the addition of recombinant CLCF1 to RANKL-stimulated monocytes resulted in a significant suppression in the number of differentiated osteoclasts with small resorption areas being observed on dentine slices in vitro. At the same dosage, CLCF1 did not exhibit any detectable negative effects on the differentiation of osteoblasts. Mechanistically, the inhibition of osteoclast differentiation by the CLCF1 treatment appears to be related to the activation of interferon signaling (IFN) and the suppression of the NF-κB signaling pathway. Interestingly, the expression of the main components of IFN-signaling namely, STAT1 and IRF1, was detected in macrophages as early as 1 h after stimulation with CLCF1. Consistent with these results, the blockade of STAT1 in macrophages abolished the inhibitory effect of CLCF1 on osteoclast differentiation in vitro. These collective findings point to a novel immunoregulatory function of CLCF1 in bone remodeling and highlight it as a potentially useful therapeutic agent for the treatment of osteoporosis.
• Association of gait with global cognitive function and cognitive domains detected by MoCA-J among community-dwelling older adults: a cross-sectional study.
  Wen Hao; Wenjing Zhao; Takashi Kimura; Shigekazu Ukawa; Ken Kadoya; Katsunori Kondo; Akiko Tamakoshi
  BMC geriatrics, 21, 1, 523, 523, 02 Oct. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: Gait was proved to be strongly associated with global cognitive function and multiple cognitive domains; however, previous research usually concentrated on individual gait parameters. This study used wearable sensors to measure gait parameters in different aspects and comprehensively explored the association of gait with global cognitive function and cognitive domains. METHODS: The data of this cross-sectional study were obtained from 236 community-dwelling Japanese older adults (125 men and 111 women) aged 70-81 years. Gait was measured by asking participants to walk a 6-m course and back using the Physilog® sensors (GaiUp®, Switzerland). Global cognitive function and cognitive domains were evaluated by face-to-face interviews using the Japanese version of the Montreal Cognitive Assessment. Twenty gait parameters were summarized as independent gait factors using factor analysis. A generalized linear model and linear regression model were used to explore the relationship of gait with global cognitive function and cognitive domains adjusted for several confounding factors. RESULTS: Factor analysis yielded four gait factors: general cycle, initial contact, propulsion, and mid-swing. Among them, general cycle factor was significantly associated with global cognitive function (β = - 0.487, [- 0.890, - 0.085]) and executive function (P = 0.049); initial contact was associated with executive function (P = 0.017). CONCLUSION: General cycle of gait might be the better marker of global cognitive function and gait is most strongly associated with executive function. The longitudinal relationships should be examined in future cohort studies.
• Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis.
  Gen Matsumae; Tomohiro Shimizu; Yuan Tian; Daisuke Takahashi; Taku Ebata; Hend Alhasan; Shunichi Yokota; Ken Kadoya; Mohamad Alaa Terkawi; Norimasa Iwasaki
  Bioengineering & translational medicine, 6, 3, e10232, Sep. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Macrophages are generally thought to play a key role in the pathogenesis of aseptic loosening through initiating periprosthetic inflammation and pathological bone resorption. The aim of this study was to identify macrophage-derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage-derived factors that were identified by RNA-seq analysis of stimulated macrophages on osteoclast differentiation. Surprisingly, thymidine phosphorylase (TYMP) was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP knockdown reduced the number of osteoclasts in macrophages that had been stimulated with polyethylene debris. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. The RNA-seq for TYMP-induced-osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris-induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis.
• 軸索再生に至適な移植細胞の同定を目的とした新しい末梢神経再建モデル
  遠藤 健; 角家 健; 鈴木 裕貴; 河村 太介; 岩崎 倫政
  北海道整形災害外科学会雑誌, 63, 1, 1, 13, 北海道整形災害外科学会, Aug. 2021
  Japanese
• Morphologic Changes in the Vertebral Artery Subsequent to Cervical Spine Degeneration and Aging: Analyses by Computed Tomography Angiography Using Multiplanar and 3-Dimensional Reconstructions
  Takashi Ohnishi; Kota Suda; Miki Komatsu; Satoko Matsumoto Harmon; Takamasa Watanabe; Mitsuru Asukai; Ken Kadoya; Masahiko Takahata; Norimasa Iwasaki; Akio Minami
  World Neurosurgery, 150, e686, e695, Elsevier BV, Jun. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVE: To identify the morphologic changes in the vertebral artery (VA) subsequent to cervical spine degeneration and aging and to investigate the risk factors for iatrogenic VA injury or occlusion. METHODS: Eighty-eight consecutive patients (176 bilateral VAs) were retrospectively analyzed using radiographs, computed tomography, and computed tomography angiography images. The Kellgren and Lawrence (KL) score and its modified subscores were used to grade the severity of degenerative changes in the cervical spine. VA tortuosity widths and diameters were measured between the C2 and C6 transverse foramens. The outcome measures were statistically analyzed for difference, correlation, and explanatory variable. The level with a high prevalence of VA stenosis was also evaluated. RESULTS: There were significant positive correlations between the KL score and VA tortuosity width, and between age and VA tortuosity width. Osteophyte formation in the facet joint was the predominant explanatory variable for medial deviation of the VA. Significant positive correlations were evident between the dominant VA diameter and KL score or age. VA stenosis occurred at C3/C4 (24.5%) with the highest prevalence and it was caused by uncovertebral joint osteophytes (52.0%) with the highest incidence. CONCLUSIONS: The present study provides important evidence for decisions of surgical strategy and for avoiding catastrophic VA injury or occlusion in cervical spine surgeries.
• Flightless I is a catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis
  Taku Ebata; Mohamad Alaa Terkawi; Masanari Hamasaki; Gen Matsumae; Tomohiro Onodera; Mahmoud Khamis Aly; Shunichi Yokota; Hend Alhasan; Tomohiro Shimizu; Daisuke Takahashi; Kentaro Homan; Ken Kadoya; Norimasa Iwasaki
  iScience, 102643, 102643, Elsevier BV, May 2021, [Peer-reviewed]
  Scientific journal
• 頸椎変性と加齢に伴い生じる椎骨動脈の形態的異常 術中椎骨動脈損傷と術後閉塞を回避するための新たなエビデンス
  大西 貴士; 須田 浩太; 小松 幹; 松本 聡子; 渡辺 尭仁; 飛鳥井 光; 角家 健; 高畑 雅彦; 東條 泰明; 神谷 行宣; 岩崎 倫政; 三浪 明男
  日本整形外科学会雑誌, 95, 3, S984, S984, (公社)日本整形外科学会, Mar. 2021
  Japanese
• 炎症性マクロファージ由来細胞外小胞が軟骨変性に及ぼす影響
  江畑 拓; Alaa Terkawi; 松前 元; 横田 隼一; Hend Alhasan; 本谷 和俊; 清水 智弘; 高橋 大介; 小野寺 智洋; 角家 健; 岩崎 倫政
  北海道整形災害外科学会雑誌, 63, 140th suppl, 62, 62, 北海道整形災害外科学会, 2021
  Japanese
• 末梢神経損傷後の好中球の時空間的変化に関する検討
  山本 康弘; 角家 健; 岩崎 倫政; 市原 理司; 石島 旨章
  北海道整形災害外科学会雑誌, 63, 139th suppl, 61, 61, 北海道整形災害外科学会, 2021
  Japanese
• 末梢神経損傷後の好中球の時空間的変化に関する検討
  山本 康弘; 角家 健; 市原 理司; 原 章; 岩崎 倫政; 金子 和夫
  末梢神経, 31, 2, 325, 325, 日本末梢神経学会, Dec. 2020
  Japanese
• Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan
  Keiko Yamada; Yoichi M. Ito; Masao Akagi; Etsuo Chosa; Takeshi Fuji; Kenichi Hirano; Shinichi Ikeda; Hideaki Ishibashi; Yasuyuki Ishibashi; Muneaki Ishijima; Eiji Itoi; Norimasa Iwasaki; Ryoichi Izumida; Ken Kadoya; Masayuki Kamimura; Arihiko Kanaji; Hiroyuki Kato; Shunji Kishida; Naohiko Mashima; Shuichi Matsuda; Yasumoto Matsui; Toshiki Matsunaga; Naohisa Miyakoshi; Hiroshi Mizuta; Yutaka Nakamura; Ken Nakata; Go Omori; Koji Osuka; Yuji Uchio; Kazuteru Ryu; Nobuyuki Sasaki; Kimihito Sato; Masuo Senda; Akihiro Sudo; Naonobu Takahira; Hiroshi Tsumura; Satoshi Yamaguchi; Noriaki Yamamoto; Kozo Nakamura; Takashi Ohe
  Journal of Orthopaedic Science, 25, 6, 1084, 1092, Elsevier BV, Nov. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.
• 人工関節術後無菌性緩みにおけるチミジンホスホリラーゼの機能と骨吸収メカニズムの解明
  松前 元; Terkawi Alaa; 木田 博朗; 江畑 拓; 田 園; Alhasan Hend; 清水 智弘; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 94, 8, S1711, S1711, (公社)日本整形外科学会, Sep. 2020
  Japanese
• 末梢神経損傷後の好中球の時空間的変化に関する検討
  山本 康弘; 角家 健; 市原 理司; 原 章; 金子 和夫; 岩崎 倫政
  日本整形外科学会雑誌, 94, 8, S1869, S1869, (公社)日本整形外科学会, Sep. 2020
  Japanese
• Blockade of XCL1/Lymphotactin Ameliorates Severity of Periprosthetic Osteolysis Triggered by Polyethylene-Particles
  Yuan Tian; Mohamad Alaa Terkawi; Tomohiro Onodera; Hend Alhasan; Gen Matsumae; Daisuke Takahashi; Masanari Hamasaki; Taku Ebata; Mahmoud Khamis Aly; Hiroaki Kida; Tomohiro Shimizu; Keita Uetsuki; Ken Kadoya; Norimasa Iwasaki
  Frontiers in Immunology, 11, 1720, 1720, Frontiers Media SA, 04 Aug. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Periprosthetic osteolysis induced by orthopedic implant-wear particles continues to be the leading cause of arthroplasty failure in majority of patients. Release of the wear debris results in a chronic local inflammatory response typified by the recruitment of immune cells, including macrophages. The cellular mediators derived from activated macrophages favor the osteoclast-bone resorbing activity resulting in bone loss at the site of implant and loosening of the prosthetic components. Emerging evidence suggests that chemokines and their receptors are involved in the progression of periprosthetic osteolysis associated with aseptic implant loosening. In the current study, we investigated the potential role of chemokine C-motif-ligand-1 (XCL1) in the pathogenesis of inflammatory osteolysis induced by wear particles. Expressions of XCL1 and its receptor XCR1 were evident in synovial fluids and tissues surrounding hip-implants of patients undergoing revision total hip arthroplasty. Furthermore, murine calvarial osteolysis model induced by ultra-high molecular weight polyethylene (UHMWPE) particles was used to study the role of XCL1 in the development of inflammatory osteolysis. Mice received single injection of recombinant XCL1 onto the calvariae after implantation of particles exhibited significantly greater osteolytic lesions than the control mice. In contrast, blockade of XCL1 by neutralizing antibody significantly reduced bone erosion and the number of bone-resorbing mature osteoclasts induced by UHMWPE particles. In consistence with the results, transplantation of XCL1-soaked sponge onto calvariae caused osteolytic lesions coincident with excessive infiltration of inflammatory cells and osteoclasts. These results suggested that XCL1 might be involved in the development of periprosthetic osteolysis through promoting infiltration of inflammatory cells and bone resorbing-osteoclasts. Our further results demonstrated that supplementing recombinant XCL1 to cultured human monocytes stimulated with the receptor activator of nuclear factor kappa-B ligand (RANKL) promoted osteoclastogenesis and the osteoclast-bone resorbing activity. Moreover, recombinant XCL1 promoted the expression of inflammatory and osteoclastogenic factors, including IL-6, IL-8, and RANKL in human differentiated osteoblasts. Together, these results suggested the potential role of XCL1 in the pathogenesis of periprosthetic osteolysis and aseptic loosening. Our data broaden knowledge of the pathogenesis of aseptic prosthesis loosening and highlight a novel molecular target for therapeutic intervention.
• 脊髄損傷治療の現状と脊髄再生-東京オリンピック、パラリンピックを記念して- 急性期病院が脊髄再生に果たすべき役割 つなぐべき希望
  須田 浩太; 松本 聡子; 小松 幹; 大西 貴士; 渡辺 尭仁; 飛鳥井 光; 宇都宮 祥弘; 東條 泰明; 三浪 明男; 角家 健; 高畑 雅彦; 岩崎 倫政
  日本整形外科学会雑誌, 94, 2, S26, S26, (公社)日本整形外科学会, Mar. 2020
  Japanese
• 分化度の異なる各種シュワン細胞の末梢神経軸索再生効果の検討
  遠藤 健; 角家 健; 鈴木 智亮; 松井 祐樹; 袁 儒非; 山本 康弘; 河村 太介; 岩崎 倫政
  末梢神経, 30, 2, 257, 257, 日本末梢神経学会, Dec. 2019
  Japanese
• 炎症収束性マクロファージ由来の新規骨吸収抑制因子の同定 骨粗鬆症に対する新たな治療法開発に向けて
  Terkawi M. Alaa; 松前 元; 田 園; Alhasan Hend; 濱崎 雅成; 江畑 拓; 高橋 大介; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 93, 8, S1834, S1834, (公社)日本整形外科学会, Sep. 2019
  Japanese
• Schwann細胞の接着因子を介した神経突起伸長効果の検討
  遠藤 健; 角家 健; 鈴木 裕貴; 松居 祐樹; 袁 儒非; 鈴木 智亮; 福井 隆史; 山本 康弘; 河村 太介; 岩崎 倫政
  日本整形外科学会雑誌, 93, 8, S1707, S1707, (公社)日本整形外科学会, Sep. 2019
  Japanese
• Evidence for cell-contact factor involvement in neurite outgrowth of DRG neurons stimulated by Schwann cells.
  Endo T; Kadoya K; Kawamura D; Iwasaki N
  Experimental physiology, 104, 10, 1447, 1454, Jul. 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, NEW FINDINGS: What is the central question of this study? Although the factors secreted from Schwann cells that promote axonal growth in the peripheral nervous system have been well studied, the effect of cell-contact factors on Schwann cells remains to be determined. What is the main finding and its importance? This study demonstrates that Schwann cells stimulate neurite outgrowth by direct contact with neurites and by secreting factors. Notably, the effect of cell-contact factors in neurite outgrowth is comparable to that of secreted factors, indicating that the identification of cell surface molecules on Schwann cells that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury. ABSTRACT: Schwann cells (SCs) play a variety of roles in the regeneration process after injury to the peripheral nervous system. The factors secreted from SCs that promote axonal growth have been well studied. However, the involvement of cell-contact factors on SCs remains to be determined. Here, we demonstrate a significant contribution of a cell-contact mechanism in the effect of SCs on promotion of neuronal outgrowth. Neurite outgrowth of adult sensory neurons from dorsal root ganglia was quantified during co-culture with adult SCs. Direct contact of SCs with neurons was eliminated by culturing SCs on an insert placed in the same well; this resulted in a 51% reduction in the length of neurite outgrowth. In addition, when dorsal root ganglion neurons were cultured on sparsely seeded SCs, neurons that made contact with SCs on their neurites had 118% longer neurites than neurons that lacked contacts with SCs. Collectively, these findings provide evidence that SCs stimulate neurite outgrowth via direct contact with neurites in addition to secreting factors. The identification of cell surface molecules on SCs that promote neurite outgrowth could lead to development of a new therapy for peripheral nervous system injury.
• シュワン細胞の接着因子を介した神経突起伸長効果の検討
  遠藤 健; 角家 健; 松居 祐樹; 袁 儒非; 鈴木 智亮; 永野 裕介; 河村 太介; 岩崎 倫政
  日本手外科学会雑誌, 36, 1, O3, 5, (一社)日本手外科学会, Apr. 2019
  Japanese
• 軸索再生に至適なシュワン細胞の分化度に関する検討
  遠藤 健; 角家 健; 鈴木 智亮; 松居 祐樹; 袁 儒非; 永野 裕介; 河村 太介; 岩崎 倫政
  日本手外科学会雑誌, 36, 1, BP2, 4, (一社)日本手外科学会, Apr. 2019
  Japanese
• Identification of IL-27 as potent regulator of inflammatory osteolysis associated with vitamin E-blended ultra-high molecular weight polyethylene debris of orthopedic implants.
  Terkawi MA; Kadoya K; Takahashi D; Tian Y; Hamasaki M; Matsumae G; Alhasan H; Elmorsy S; Uetsuki K; Onodera T; Takahata M; Iwasaki N
  Acta biomaterialia, 89, 242, 251, Apr. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Vitamin E-blended ultra-high molecular weight polyethylene (VE-UHMWPE) is a newly introduced material for prosthetic components that has proven a better mechanical performance with lesser adverse cellular responses than conventional polyethylene in experimental animal models. However, the mechanisms by which VE-UHMWPE particles trigger a reduced osteolytic activity are unclear and remain to be investigated. Therefore, the current study aims at exploring a possible anti-osteolytic mechanism associated with VE-UHMWPE particles. Transcriptional profiling and bioinformatic analyses of human macrophages stimulated by VE-UHMWPE particles revealed a distinct transcriptional program from macrophages stimulated with UHMWPE particles. Out of the up-regulated genes, IL-27 was found to be significantly elevated in macrophages cultured with VE-UHMWPE particles as compared to these with UHMWPE particles (p = 0.0084). Furthermore, we studied the potential anti-osteolytic function of IL-27 in osteolysis murine model. Interestingly, administration of recombinant IL-27 onto calvariae significantly alleviated osteolytic lesions triggered by UHMWPE particles (p = 0.0002). Likewise, IL-27 inhibited differentiation of osteoclasts (p = 0.0116) and reduced inflammatory response (p < 0.0001) elicited by conventional UHMWPE particles in vitro. This is the first study demonstrating the involvement of IL-27 in macrophage response to VE-UHMWPE particles and its regulatory role in osteolysis. Our data highlight a novel therapeutic agent for treatment of inflammatory osteolysis induced by polyethylene debris. STATEMENT OF SIGNIFICANCE: Aseptic loosening due to inflammatory osteolysis remains the major cause of arthroplasty failure and represents a substantial economic burden worldwide. Ideal approach to prevent this failure should be directed to minimize inflammatory response triggered by wear particles at the site of implant. Understanding the mechanism by which VE-UHMWPE particles triggers lesser cellular responses and reduced osteolysis as compared to conventional UHMWPE particles may aid in discovery of regulatory factors. In the current study, we reported that IL-27 is a potent regulator of inflammatory osteolysis involved in the reduced biologic activities and osteolytic potentials associated with VE-UHMWPE particles. Initiating the production IL-27 in vivo after total joint arthroplasties might be a novel strategy to prolong the life-spam of implant.
• 悪性腫瘍の脊椎直接浸潤に対する脊椎摘出術を行った症例について
  岩田 玲; 高畑 雅彦; 須藤 英毅; 角家 健; 山田 勝久; 遠藤 努; 大西 貴士
  北海道整形災害外科学会雑誌, 60, 2, 263, 263, 北海道整形災害外科学会, Mar. 2019
  Japanese
• 合併症を生じやすい脊椎腫瘍手術の条件
  岩田 玲; 高畑 雅彦; 角家 健; 須藤 英毅; 山田 勝久; 遠藤 努; 大西 貴士; 伊東 学; 鐙 邦芳; 岩崎 倫政
  Journal of Spine Research, 10, 3, 272, 272, (一社)日本脊椎脊髄病学会, Mar. 2019
  Japanese
• Regenerating Corticospinal Axons Innervate Phenotypically Appropriate Neurons within Neural Stem Cell Grafts.
  Kumamaru H; Lu P; Rosenzweig ES; Kadoya K; Tuszynski MH
  Cell reports, 26, 9, 2329, 2339.e4, Feb. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Neural progenitor cell grafts form new relays across sites of spinal cord injury (SCI). Using a panel of neuronal markers, we demonstrate that spinal neural progenitor grafts to sites of rodent SCI adopt diverse spinal motor and sensory interneuronal fates, representing most neuronal subtypes of the intact spinal cord, and spontaneously segregate into domains of distinct cell clusters. Host corticospinal motor axons regenerating into neural progenitor grafts innervate appropriate pre-motor interneurons, based on trans-synaptic tracing with herpes simplex virus. A human spinal neural progenitor cell graft to a non-human primate also received topographically appropriate corticospinal axon regeneration. Thus, grafted spinal neural progenitor cells give rise to a variety of neuronal progeny that are typical of the normal spinal cord; remarkably, regenerating injured adult corticospinal motor axons spontaneously locate appropriate motor domains in the heterogeneous, developing graft environment, without a need for additional exogenous guidance.
• 炎症性骨溶解及び骨吸収におけるNOV(Nephroblastoma overexpressed)の機能解析
  松前 元; テルカウィ・アラー; 田 園; 濱崎 雅成; ヘンド・アルハサン; 江畑 拓; 高橋 大介; 角家 健; 岩崎 倫政
  北海道整形災害外科学会雑誌, 61, 136th suppl, 29, 29, 北海道整形災害外科学会, 2019
  Japanese
• シュワン細胞の接着因子を介した神経突起伸長効果の検討
  遠藤 健; 角家 健; 鈴木 裕貴; 松居 祐樹; 袁 儒非; 鈴木 智亮; 福井 隆史; 山本 康弘; 河村 太介; 岩崎 倫政
  北海道整形災害外科学会雑誌, 61, 136th suppl, 88, 88, 北海道整形災害外科学会, 2019
  Japanese
• 転移性脊椎腫瘍術後合併症の危険因子
  岩田 玲; 山田 勝久; 遠藤 努; 大西 貴士; 角家 健; 高畑 雅彦; 岩崎 倫政; 須藤 英毅
  北海道整形災害外科学会雑誌, 61, 136th suppl, 8, 8, 北海道整形災害外科学会, 2019
  Japanese
• A Novel Experimental Model to Determine the Axon-Promoting Effects of Grafted Cells After Peripheral Nerve Injury.
  Endo T; Kadoya K; Suzuki Y; Kawamura D; Iwasaki N
  Frontiers in cellular neuroscience, 13, 280, 280, 2019, [Peer-reviewed], [Corresponding author], [International Magazine]
  English, Scientific journal, Although peripheral nerves can regenerate, clinical outcomes after peripheral nerve injuries are not always satisfactory, especially in cases of severe or proximal injuries. Further, autologous nerve grafting remains the gold standard for the reconstruction of peripheral nerves, although this method is still accompanied by issues of donor-site morbidity and limited supply. Cell therapy is a potential approach to overcome these issues. However, the optimal cell type for promoting axon regeneration remains unknown. Here, we report a novel experimental model dedicated to elucidation of the axon-promoting effects of candidate cell types using simple and standardized techniques. This model uses rat sciatic nerves and consists of a 25 mm-long acellular region and a crush site at each end. The acellular region was made by repeated freeze/thaw procedures with liquid nitrogen. Importantly, the new model does not require microsurgical procedures, which are technically demanding and greatly affect axon regeneration. To test the actual utility of this model, red fluorescent protein-expressing syngeneic Schwann cells (SCs), marrow stromal cells, or fibroblasts were grafted into the acellular area, followed by perfusion of the rat 2 weeks later. All types of grafted cells survived well. Quantification of regenerating axons demonstrated that SCs, but not the other cell types, promoted axon regeneration with minimum variability. Thus, this model is useful for differentiating the effects of various grafted cell types in axon regeneration. Interestingly, regardless of the grafted cell type, host SCs migrated into the acellular area, and the extent of axon regeneration was strongly correlated with the number of SCs. Moreover, all regenerating axons were closely associated with SCs. These findings suggest a critical role for SCs in peripheral nerve axon regeneration. Collectively, this novel experimental model is useful for elucidating the axon-promoting effects of grafted cells and for analyzing the biology of peripheral nerve axon regeneration.
• 分化度の異なる各種シュワン細胞の末梢神経軸索再生効果の検討
  遠藤 健; 角家 健; 永野 裕介; 河村 大介; 岩崎 倫政
  末梢神経, 29, 2, 253, 253, 日本末梢神経学会, Dec. 2018
  Japanese
• Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts
  Jennifer N. Dulin; Andrew F. Adler; Hiromi Kumamaru; Gunnar H. D. Poplawski; Corinne Lee-Kubli; Hans Strobl; Daniel Gibbs; Ken Kadoya; James W. Fawcett; Paul Lu; Mark H. Tuszynski
  Nature Communications, 9, 1, 84, Nature Publishing Group, 01 Dec. 2018, [Peer-reviewed]
  English, Scientific journal
• Generation and post-injury integration of human spinal cord neural stem cells.
  Kumamaru H; Kadoya K; Adler AF; Takashima Y; Graham L; Coppola G; Tuszynski MH
  Nature methods, 15, 9, 723, 731, Sep. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Spinal cord neural stem cells (NSCs) have great potential to reconstitute damaged spinal neural circuitry, but they have yet to be generated in vitro. We now report the derivation of spinal cord NSCs from human pluripotent stem cells (hPSCs). Our observations show that these spinal cord NSCs differentiate into a diverse population of spinal cord neurons occupying multiple positions along the dorso-ventral axis, and can be maintained for prolonged time periods. Grafts into injured spinal cords were rich with excitatory neurons, extended large numbers of axons over long distances, innervated their target structures, and enabled robust corticospinal regeneration. The grafts synaptically integrated into multiple host intraspinal and supraspinal systems, including the corticospinal projection, and improved functional outcomes after injury. hPSC-derived spinal cord NSCs could enable a broad range of biomedical applications for in vitro disease modeling and constitute an improved clinically translatable cell source for 'replacement' strategies in several spinal cord disorders.
• 末梢神経の軸索再生はシュワン細胞の分布量と相関する
  遠藤 健; 角家 健; 鈴木 裕貴; 岩崎 倫政
  北海道整形災害外科学会雑誌, 60, 1, 143, 144, 北海道整形災害外科学会, Aug. 2018
  Japanese
• 分化度の異なる各種Schwann細胞の末梢神経軸索再生効果の検討
  遠藤 健; 角家 健; 鈴木 裕貴; 松居 祐樹; 袁 儒非; 永野 裕介; 河村 太介; 岩崎 倫政
  日本整形外科学会雑誌, 92, 8, S1961, S1961, (公社)日本整形外科学会, Aug. 2018
  Japanese
• 第5腰椎骨腫瘍摘出術における腸骨稜切離飜転による椎骨側方アプローチの有用性
  岩田 玲; 高畑 雅彦; 須藤 英毅; 角家 健; 山田 勝久; 大西 貴士; 岩崎 倫政
  東日本整形災害外科学会雑誌, 30, 3, 353, 353, 東日本整形災害外科学会, Aug. 2018
  Japanese
• Restorative effects of human neural stem cell grafts on the primate spinal cord
  Ephron S Rosenzweig; John H Brock; Paul Lu; Hiromi Kumamaru; Ernesto A Salegio; Ken Kadoya; Janet L Weber; Justine J Liang; Rod Moseanko; Stephanie Hawbecker; J Russell Huie; Leif A Havton; Yvette S Nout-Lomas; Adam R Ferguson; Michael S Beattie; Jacqueline C Bresnahan; Mark H Tuszynski
  Nature Medicine, 24, 4, 484, 490, Nature Publishing Group, 01 May 2018, [Peer-reviewed]
  English, Scientific journal
• AxonTracer: A novel ImageJ plugin for automated quantification of axon regeneration in spinal cord tissue
  Akash Patel; Zhongzhi Li; Philip Canete; Hans Strobl; Jennifer Dulin; Ken Kadoya; Dan Gibbs; Gunnar H.D. Poplawski
  BMC Neuroscience, 19, 1, 8, BioMed Central Ltd., 09 Mar. 2018, [Peer-reviewed]
  English, Scientific journal
• 新規末梢神経軸索再生評価モデルが明らかにするシュワン細胞の軸索再生効果 骨髄間葉系幹細胞との比較
  遠藤 健; 角家 健; 岩崎 倫政
  北海道整形災害外科学会雑誌, 59, 2, 248, 249, 北海道整形災害外科学会, Mar. 2018
  Japanese
• 分化度の異なる各種シュワン細胞の末梢神経軸索再生効果の検討
  遠藤 健; 角家 健; 鈴木 裕貴; 松居 祐樹; 袁 儒非; 永野 裕介; 河村 太介; 岩崎 倫政
  北海道整形災害外科学会雑誌, 60, 135th suppl, 23, 23, 北海道整形災害外科学会, 2018
  Japanese
• 第5腰椎摘出術における脊柱起立筋付き腸骨 切離翻転による後方からの椎体側方剥離操作への有用性
  岩田 玲; 高畑 雅彦; 須藤 英毅; 角家 健; 山田 勝久; 遠藤 努; 大西 貴士; 岩崎 倫政
  北海道整形災害外科学会雑誌, 60, 135th suppl, 70, 70, 北海道整形災害外科学会, 2018
  Japanese
• 脊椎および骨盤への悪性腫瘍の直接浸潤に対する腫瘍全摘出術の報告
  岩田 玲; 高畑 雅彦; 須藤 英毅; 角家 健; 山田 勝久; 遠藤 努; 大西 貴士; 岩崎 倫政
  北海道整形災害外科学会雑誌, 60, 135th suppl, 70, 70, 北海道整形災害外科学会, 2018
  Japanese
• Transcriptional profile of human macrophages stimulated by ultra-high molecular weight polyethylene particulate debris of orthopedic implants uncovers a common gene expression signature of rheumatoid arthritis
  Mohamad Alaa Terkawi; Masanari Hamasaki; Daisuke Takahashi; Masahiro Ota; Ken Kadoya; Tomoyo Yutani; Keita Uetsuki; Tsuyoshi Asano; Tohru Irie; Ryuta Arai; Tomohiro Onodera; Masahiko Takahata; Norimasa Iwasaki
  Acta Biomaterialia, 65, 417, 425, Acta Materialia Inc, 01 Jan. 2018, [Peer-reviewed]
  English, Scientific journal
• 新規末梢神経再建モデルが明らかにした軸索再生におけるシュワン細胞の重要性
  遠藤 健; 角家 健; 岩崎 倫政
  末梢神経, 28, 2, 274, 274, 日本末梢神経学会, Dec. 2017
  Japanese
• Effective Repair of Dural Tear Using Bioabsorbable Sheet With Fibrin Glue
  Akira Iwata; Masahiko Takahata; Ken Kadoya; Hideaki Sudo; Terufumi Kokabu; Katsuhisa Yamada; Norimasa Iwasaki
  SPINE, 42, 18, 1362, 1366, Sep. 2017, [Peer-reviewed]
  English, Scientific journal
• In situ freeze and thaw法を用いた新しい末梢神経損傷モデル 軸索再生に至適な移植細胞同定のために
  遠藤 健; 角家 健; 岩崎 倫政
  北海道整形災害外科学会雑誌, 59, 1, 105, 105, 北海道整形災害外科学会, Aug. 2017
  Japanese
• 新規末梢神経再建モデルが明らかにした軸索再生におけるSchwann細胞の重要性
  遠藤 健; 角家 健; 鈴木 裕貴; 岩崎 倫政
  日本整形外科学会雑誌, 91, 8, S1788, S1788, (公社)日本整形外科学会, Aug. 2017
  Japanese
• Comprehensive Monosynaptic Rabies Virus Mapping of Host Connectivity with Neural Progenitor Grafts after Spinal Cord Injury
  Andrew F. Adler; Corinne Lee-Kubli; Hiromi Kumamaru; Ken Kadoya; Mark H. Tuszynski
  STEM CELL REPORTS, 8, 6, 1525, 1533, Jun. 2017, [Peer-reviewed]
  English, Scientific journal
• In situ freeze and thaw法を用いた新しい末梢神経損傷モデル 軸索再生に至適な移植細胞同定のために
  遠藤 健; 角家 健; 岩崎 倫政
  末梢神経, 27, 2, 275, 275, 日本末梢神経学会, Dec. 2016
  Japanese
• In situ freeze and thaw法を用いた新しい末梢神経損傷モデル 軸索再生に至適な移植細胞同定のために
  遠藤 健; 角家 健; 岩崎 倫政
  日本整形外科学会雑誌, 90, 8, S1548, S1548, (公社)日本整形外科学会, Aug. 2016
  Japanese
• Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration
  Ken Kadoya; Paul Lu; Kenny Nguyen; Corinne Lee-Kubli; Hiromi Kumamaru; Lin Yao; Joshua Knackert; Gunnar Poplawski; Jennifer N. Dulin; Hans Strob; Yoshio Takashima; Jeremy Biane; James Conner; Su-Chun Zhang; Mark H. Tuszynski
  NATURE MEDICINE, 22, 5, 479, 487, May 2016, [Peer-reviewed]
  English, Scientific journal
• Axonal growth and connectivity from neural stem cell grafts in models of spinal cord injury
  Paul Lu; Ken Kadoya; Mark H. Tuszynski
  CURRENT OPINION IN NEUROBIOLOGY, 27, 103, 109, Aug. 2014, [Peer-reviewed]
  English, Scientific journal
• Combined Intrinsic and Extrinsic Neuronal Mechanisms Facilitate Bridging Axonal Regeneration One Year after Spinal Cord Injury
  Ken Kadoya; Shingo Tsukada; Paul Lu; Giovanni Coppola; Dan Geschwind; Marie T. Filbin; Armin Blesch; Mark H. Tuszynski
  NEURON, 64, 2, 165, 172, Oct. 2009, [Peer-reviewed]
  English, Scientific journal
• Efficient retrograde neuronal transduction utilizing self-complementary AAV1
  Edmund R. Hollis; Ken Kadoya; Matthew Hirsch; Richard J. Samulski; Mark H. Tuszynski
  MOLECULAR THERAPY, 16, 2, 296, 301, Feb. 2008, [Peer-reviewed]
  English, Scientific journal
• Efficient retrograde neuronal transduction utilizing self-complementary AAV1
  Edmund R. Hollis; Ken Kadoya; Matthew Hirsch; Richard J. Samulski; Mark H. Tuszynski
  MOLECULAR THERAPY, 16, 2, 296, 301, Feb. 2008, [Peer-reviewed]
  English, Scientific journal
• Effect of Hydroxyapatite porous characteristics on healing outcomes in rabbit posterolateral spinal fusion model
  Makoto Motomiya; Manabu Ito; Masahiko Takahata; Ken Kadoya; Kazuharu Irie; Kuniyoshi Abumi; Akio Minami
  EUROPEAN SPINE JOURNAL, 16, 12, 2215, 2224, Dec. 2007, [Peer-reviewed]
  English, Scientific journal
• Clinical outcome of posterolateral endoscopic surgery for pyogenic spondylodiscitis - Results of 15 patients with serious comorbid conditions
  Manabu Ito; Kuniyoshi Abumi; Yoshihisa Kotani; Ken Kadoya; Akio Minami
  SPINE, 32, 2, 200, 206, Jan. 2007, [Peer-reviewed]
  English, Scientific journal
• Vertebral osteonecrosis associated with sarcoidosis - Case report
  M Ito; M Motomiya; K Abumi; O Shirado; Y Kotani; K Kadoya; E Murota; A Minami
  JOURNAL OF NEUROSURGERY-SPINE, 2, 2, 222, 225, Feb. 2005, [Peer-reviewed]
  English, Scientific journal
• Vertebral osteonecrosis associated with sarcoidosis. Case report.
  Ito M; Motomiya M; Abumi K; Shirado O; Kotani Y; Kadoya K; Murota E; Minami A
  Journal of neurosurgery. Spine, 2, 2, 222, 225, Feb. 2005, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Sarcoidosis is a systemic disease commonly affecting lung, skin, or eye. Sarcoidosis involved with osseous structures occurs in approximately 5% of patients, usually involving small bones. Spinal sarcoidosis is extremely rare. The authors report on a man in whom examination of a subclavicular lymph node biopsy specimen and its spinal involvement had established a diagnosis of sarcoidosis and who had undergone steroid therapy. Despite intensive conservative treatment, the authors observed progressive collapse of L-2 requiring spinal decompressive and reconstructive surgeries. Histological evaluation of the collapsed vertebra did not show the typical noncaseating granuloma; rather, the authors observed osteonecrosis of the entire L-2 structure without reactive cellular activities. Other potential diagnoses including infectious disease, metastatic spinal tumor, and osteoporotic vertebral collapse were excluded based on laboratory data, imaging studies, and pathological findings. Complete necrosis of the entire L-2 vertebra in this case can be considered as a rare clinical manifestation of spinal sarcoidosis. Because of osteopenia and systemic bone fragility, combined anterior-posterior spinal reconstructive surgery was performed to restabilize the severely damaged spine.
• Two-year observation of artificial intervertebral disc replacement: results after supplemental ultra-high strength bioresorbable spinal stabilization
  Y Kotani; K Abumi; Y Shikinami; M Takahata; K Kadoya; T Kadosawa; A Minami; K Kaneda
  JOURNAL OF NEUROSURGERY, 100, 4, 337, 342, Apr. 2004, [Peer-reviewed]
  English, Scientific journal
• Static and dynamic analysis of five anterior instrumentation systems for thoracolumbar scoliosis
  N Shimamoto; Y Kotani; Y Shono; K Kadoya; K Abumi; A Minami; K Kaneda
  SPINE, 28, 15, 1678, 1685, Aug. 2003, [Peer-reviewed]
  English, Scientific journal
• Artificial intervertebral disc replacement using bioactive three-dimensional fabric - Design, development, and preliminary animal study
  Y Kotani; K Abumi; Y Shikinami; T Takada; K Kadoya; N Shimamoto; M Ito; T Kadosawa; T Fujinaga; K Kaneda
  SPINE, 27, 9, 929, 935, May 2002, [Peer-reviewed]
  English, Scientific journal
• Biomechanical evaluation of anterior spinal instrumentation systems for scoliosis - In vitro fatigue simulation
  N Shimamoto; Y Kotani; Y Shono; K Kadoya; K Abumi; K Kaneda; A Minami
  SPINE, 26, 24, 2701, 2708, Dec. 2001, [Peer-reviewed]
  English, Scientific journal
• Biomechanical and morphologic evaluation of a three-dimensional fabric sheep artificial intervertebral disc - In vitro and in vivo analysis
  K Kadoya; Y Kotani; K Abumi; T Takada; N Shimamoto; Y Shikinami; T Kadosawa; K Kaneda
  SPINE, 26, 14, 1562, 1569, Jul. 2001, [Peer-reviewed]
  English, Scientific journal

• 再生医療応用を見据えた継代に伴う糖鎖抗原の変化と自家細胞における免疫応答の検討
  宝満健太郎; 宝満健太郎; 宝満健太郎; 徳廣泰貴; 小野寺智洋; 花松久寿; 古川潤一; 江畑拓; TERKAWI Alaa; 松岡正剛; 角家健; 岩崎倫政; 岩崎倫政; 岩崎倫政, 日本整形外科学会雑誌(CD-ROM), 99, 3, 2025
• Novel gait analysis system by gait movie with artificial intelligence: identification of gait disturbance by anterior cruciate ligament injury
  宝満健太郎; 角家健; 三宅賢稔; 田中毅; 堀脇一樹; 岩崎倫政, 整形外科, 76, 6, 2025
• 継代細胞における糖鎖シグネチャーの解明
  宝満健太郎; 徳廣泰貴; 小野寺智洋; 江畑拓; ALAA Terkawi; 松岡正剛; 花松久寿; 古川潤一; 角家健; 岩崎倫政, 北海道整形災害外科学会, 143rd, 2024
• 歩行撮影とAIを使用した新規補助診断方法の開発:腰部脊柱管狭窄症での検討 Gait based prediction of lumbar spinal stenosis using artificial intelligence
  角家健; 宝満健太郎; 三宅賢稔; 宝満健太郎; 岩崎倫政; 三宅賢稔; 中川弘充; 田中毅; 堀脇一樹; 大越康充; 松野丈夫; 武田直樹; 須田浩太, 北海道整形災害外科学会, 143rd, 2024
• 骨格情報と人工知能を活用した新規歩行解析方法-膝前十字靱帯損傷の鑑別-
  宝満健太郎; 角家健; 三宅賢稔; 三宅賢稔; 三谷雄輝; 石田直樹; 堀脇一樹; 中川弘充; 田中毅; 片岸誠; 禰寝義人; 禰寝義人; 岩崎倫政, 日本整形外科学会雑誌, 98, 2, 2024
• 慢性絞扼性神経障害の新規動物モデル開発と病態解明
  山本 康弘; 角家 健; 内藤 聖人; 石島 旨章, 日本手外科学会雑誌, 40, 1, O20, 6, Apr. 2023
  (一社)日本手外科学会, Japanese
• 足部ウェアラブルデバイスによる歩行解析の妥当性と臨床研究の実際
  角家健; 宝満健太郎; 岩崎倫政, 日本臨床スポーツ医学会誌, 31, 4, 2023
• 深度カメラと機械学習の応用による全身を対象とした歩行解析-前十字靱帯再建術後の歩行識別の試み-
  宝満健太郎; 角家健; 三宅賢稔; 三宅賢稔; 浮城健吾; 福井大輔; 中川弘充; 田中毅; 片岸誠; 大越康充; 禰寝義人; 岩崎倫政, 日本整形外科学会雑誌, 97, 8, 2023
• 全身を対象とした動作解析によるACL再建者の歩行識別:深度カメラと機械学習の応用
  宝満健太郎; 岩崎倫政; 角家健; 三宅賢稔; 三宅賢稔; 片岸誠; 禰寝義人; 浮城健吾; 井上貴博; 大越康充; 福井大輔; 中川弘充; 田中毅, 北海道整形災害外科学会, 142nd, 2023
• 歩行撮影とAIを使用した変形性膝関節症の新規診断方法の開発
  角家健; 宝満健太郎; 三宅賢稔; 三宅賢稔; 浮城健吾; 福井大輔; 中川弘充; 田中毅; 深水竜介; 大越康充; 禰寝義人; 岩崎倫政, 日本整形外科学会雑誌, 97, 2, 2023
• VCP化合物による脊髄損傷後血液脊髄関門機能保護作用
  鈴木 裕貴; 角家 健; 五月女 慧人; 遠藤 健; 船木 智; 周東 智; 前仲 勝実; 岩崎 倫政, 日本整形外科学会雑誌, 96, 8, S1631, S1631, Sep. 2022
  (公社)日本整形外科学会, Japanese
• 次硝酸ビスマスの急性期脊髄損傷に対する神経保護効果とその機序の解明
  五月女 慧人; 角家 健; 鈴木 裕貴; 遠藤 健; 中川 慎介; 前仲 勝実; 岩崎 倫政, 日本整形外科学会雑誌, 96, 8, S1691, S1691, Sep. 2022
  (公社)日本整形外科学会, Japanese
• 歩行撮影と機械学習を使用した変形性膝関節症の新規診断方法の開発
  角家健; 宝満健太郎; 三宅賢稔; 三宅賢稔; 浮城健吾; 福井大輔; 中川弘充; 田中毅; 深水竜介; 大越康充; 禰寝義人; 岩崎倫政, 日本整形外科学会雑誌, 96, 8, 2022
• Gait analysis by foot wearable device: its validity and application for clinical study
  角家健; 宝満健太郎; 岩崎倫政, 日本関節病学会誌(Web), 41, 3, 2022
• 歩行撮影とAIを使用した運動器疾患診断方法の開発
  角家健; 宝満健太郎; 三宅賢稔; 三宅賢稔; 浮城健吾; 福井大輔; 中川弘充; 田中毅; 深水竜介; 大越康充; 禰寝義人; 岩崎倫政, 日本骨代謝学会学術集会プログラム抄録集(CD-ROM), 40th, 2022
• 歩行撮影とAIを使用した変形性膝関節症の新規診断方法の開発
  角家健; 三宅賢稔; 宝満健太郎; 岩崎倫政; 三宅賢稔; 深水竜介; 禰寝義人; 浮城健吾; 大越康充; 福井大輔; 中川弘; 田中毅, 北海道整形災害外科学会, 141st, 2022
• 平滑筋弛緩薬パパベリンの新規効能:血液脊髄関門保護を介した脊髄損傷に対する神経保護効果
  鈴木裕貴; 角家健; 五月女慧人; 遠藤健; 浅野毅; 前仲勝実; 中川慎介; 岩崎倫政, 日本整形外科学会雑誌, 96, 2, 2022
• 変形性膝関節症の新規スクリーニング方法の開発-歩行撮影による歩行解析-
  角家健; 宝満健太郎; 浮城健吾; 三宅賢稔; 三宅賢稔; 深水竜介; 禰寝義人; 大越康充; 岩崎倫政, 日本整形外科学会雑誌, 96, 2, 2022
• 末梢神経損傷後の好中球浸潤の詳細 時空間的検討と血液神経関門機能との関連
  山本 康弘; 角家 健; 市原 理司; 原 章; 石島 旨章; 金子 和夫; 岩崎 倫政, 日本手外科学会雑誌, 38, 1, O8, 01, Apr. 2021
  (一社)日本手外科学会, Japanese
• 末梢神経損傷後の好中球浸潤の詳細 時空間的検討と血液神経関門機能との関連
  山本 康弘; 角家 健; 市原 理司; 原 章; 高木 辰哉; 岩崎 倫政; 金子 和夫, 日本整形外科学会雑誌, 95, 3, S882, S882, Mar. 2021
  (公社)日本整形外科学会, Japanese
• 10m直線歩行と制限のない歩行の比較研究:足部時空間パラメータによる検討
  種田健二; 角家健; 宝満健太郎; 青山誠; 大野和則; 菅原誠; 浮城健吾; 大越康允; 須田浩太; 岩崎倫政, JOSKAS-JOSSM (Web), 2021, 2021
• 平滑筋弛緩薬パパベリンの新規効能:血液脊髄関門保護を介した脊髄損傷に対する神経保護効果
  鈴木裕貴; 角家健; 五月女慧人; 遠藤健; 浅野毅; 岩崎倫政; 中川慎介; 前仲勝実, 北海道整形災害外科学会, 139th, 2, S73, S73, 2021
  (公社)日本整形外科学会, Japanese
• 歩行動画によるロコモ評価システムの開発
  角家健; 山本強; 宝満健太郎; 岩崎倫政, 医科学応用研究財団研究報告(CD-ROM), 38, 2021
• 歩行解析研究に汎用される10m直線歩行は普段の歩行を代表しているか-足部時空間パラメーターによる検討-
  角家健; 種田健二; 宝満健太郎; 須田浩太; 松本聡子; 石田直樹; 武田直樹; 大越康充; 大野和則; 菅原誠; 三浪明男; 岩崎倫政, 日本整形外科学会雑誌, 95, 2, 2021
• 歩行解析研究に汎用される10m直線歩行は普段の歩行を代表しているか?:足部時空間パラメータによる検討
  角家健; 宝満健太郎; 岩崎倫政; 種田健二; 須田浩太; 松本聡子; 三浪明男; 石田直樹; 武田直樹; 大越康充; 大野和則; 菅原誠, 北海道整形災害外科学会, 139th, 2021
• Drug development for spinal cord injury by targeting protection of blood-spinal cord barrier
  鈴木裕貴; 角家健; 遠藤健; 袁儒非; 浅野毅; 前仲勝実; 中川慎介; 岩崎倫政, Journal of Spine Research (Web), 11, 3, 2020
• 片麻痺患者の杖歩行時の足部時空間パラメータに関する検討
  宝満健太郎; 角家健; 斉藤貴志; 佐伯拓馬; 石田直樹; 岩崎倫政, 運動器リハビリテーション, 30, 2, 195, 195, 06 Jun. 2019
  日本運動器科学会, Japanese
• Validation of the Wearable Sensor System Estimating Spatiotemporal Gait Parameters by Simultaneous 3D Optical Motion Analysis.
  Kentaro Homan; Ken Kadoya; Keizo Yamamoto; Norimasa Iwasaki, The 65th Annual Meeting of Orthopaedic Research Society (ORS), 44, PS1-054, Feb. 2019
  English
• 歩行動画によるロコモ評価システムの開発
  角家 健; 山本 強; 宝満 健太郎; 岩崎 倫政, 医科学応用研究財団研究報告, 38, 58, 60, 2019
  鈴木謙三記念医科学応用研究財団, Japanese
• 足部ウェアラブルセンサシステムで算出される時空間歩行パラメータの妥当性検証
  宝満健太郎; 角家健; 岩崎倫政; 山本敬三, 北海道整形災害外科学会, 136th, 136th suppl, 90, 90, 2019
  北海道整形災害外科学会, Japanese
• ウェアラブルシステムを使用した慢性期片麻痺患者の歩行解析
  斉藤貴志; 佐伯拓馬; 五十嵐大貴; 宝満健太郎; 角家健; 岩崎倫政; 石田直樹, 北海道整形災害外科学会, 136th, 136th suppl, 91, 91, 2019
  北海道整形災害外科学会, Japanese
• 客観的に歩行パラメーターを測定する足部ウェアラブルセンサの有効性
  宝満健太郎; 角家健; 山本敬三; 岩崎倫政, 日本整形外科学会雑誌, 92, 8, S2048, S2048, 30 Aug. 2018
  (公社)日本整形外科学会, Japanese
• 北海道における整形外科基礎研究 基礎研究体制と概要 北海道大学整形外科
  角家 健; 近藤 英司; 高畑 雅彦; 須藤 英毅; 古川 潤一; 小野寺 智洋; アラー・テルカウイ; 岩崎 倫政, 北海道整形災害外科学会雑誌, 59, 2, 197, 204, Mar. 2018
  北海道整形災害外科学会, Japanese
• BDNF Gene Delivery for Alzheimer's Disease
  Mark H. Tuszynski; Krystof Bankiewicz; John Bringas; Imre Kovacs; Alan Nagahara; Jacob Koffler; Ken Kadoya, ANNALS OF NEUROLOGY, 82, S145, S145, Oct. 2017
  English, Summary international conference
• 学術奨励賞・受賞記念論文 神経前駆細胞移植による脊髄損傷後の皮質脊髄路の再生
  角家 健; Tuszynski Mark; 岩崎 倫政, 北海道整形災害外科学会雑誌 : 北海道整形災害外科学会機関誌, 59, 1, 1, 5, Aug. 2017
  北海道整形災害外科学会, Japanese
• 超高分子ポリエチレン摩耗粉によるヒトマクロファージの遺伝子発現変化は関節リウマチと類似する
  Terkawi Alaa; 濱崎 雅成; 高橋 大介; 角家 健; 浅野 毅; 入江 徹; 小野寺 智洋; 高畑 雅彦; 岩崎 倫政, 日本整形外科学会雑誌, 91, 8, S1722, S1722, Aug. 2017
  (公社)日本整形外科学会, Japanese
• Progress and Setbacks in the Study of CNS Axonal Plasticity and Regeneration
  Mark H. Tuszynski; Ken Kadoya; Paul Lu; Armin Blesch; Ephron Rosenzweig; John Brock; Karin Loew, FASEB JOURNAL, 24, Apr. 2010
  English, Summary international conference
• 脊髄損傷におけるT細胞活性化の役割-CTLA 4-Igによる補助シグナルブロック
  永野裕介; 角家健; 眞島任史; 岩崎倫政; 本宮真; 三浪明男; 今重之; 上出利光, 移植, 41, 2, 2006
• 脊髄損傷におけるT細胞活性化の役割-CTLA4-Igによる補助シグナルブロック-
  永野裕介; 角家健; 本宮真; 三浪明男; 今重之; 上出利光, 日本整形外科学会雑誌, 79, 8, 2005
• Surgical Outcome of the Corpectomy or Total Vertebrectomy for Metastatic Spinal Tumors
  TAKEDA Naoki; KOTANI Yoshihisa; KADOYA Ken; ITO Manabu; SHIRADO Osamu; MINAMI Akio; ABUMI Kuniyoshi; TANEICHI Hiroshi; KANEDA Kiyoshi, 日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association, 78, 10, 711, 716, 25 Oct. 2004
  日本整形外科学会, Japanese
• 外傷性腕神経損傷後に発生した巨大偽性髄膜りゅうの一例
  久田幸由; 小谷善久; 鐙邦芳; 伊東学; 角家健; 白土修; 三浪明男; 寺江聡, 北海道整形災害外科学会雑誌, 46, 1, 26, 10 Sep. 2004
  Japanese
• Pathology and surgical treatment for haemodialysis related spinal disorders
  ITO M., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 15, 1, 96, 96, 20 May 2004
  Japanese
• Accuracy analysis of pedicle screw placement in posterior scoliosis surgery : Comparison between manual and computer-assisted technique
  KOTANI Y., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 15, 1, 251, 251, 20 May 2004
  Japanese
• Pathology and surgical treatment of atlantoaxial rotatory fixation after failure of conservative treatment
  KADOYA K., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 15, 1, 300, 300, 20 May 2004
  Japanese
• Two-year observation of artificial intervertebral disc replacement: results after supplemental ultra-high strength bioresorbable spinal stabilization.
  Kotani Yoshihisa; Abumi Kuniyoshi; Shikinami Yasuo; Takahata Masahiko; Kadoya Ken; Kadosawa Tsuyoshi; Minami Akio; Kaneda Kiyoshi, Journal of Neurosurgery : Spine, 100, 4, 337, 342, Apr. 2004
  OBJECT: This 2-year experimental study was conducted to investigate the efficacy of a bioactive three-dimensional (3D) fabric disc for lumbar intervertebral disc replacement. The authors used a bioresorbable spinal fixation rod consisting of a forged composite of particulate unsintered hydroxyapatite/poly-L-lactide acid (HA/PLLA) for stability augmentation. The biomechanical and histological alterations as well as possible device-related loosening were examined at 2 years postoperatively. METHODS: Two lumbar intervertebral discs (L2-3 and L4-5) were replaced with the 3D fabric discs, which were augmented by two titanium screws and a spanning bioresorbable rod (HA/PLLA). The segmental biomechanics and interface bone ingrowth were investigated at 6, 15, and 24 months postoperatively, and results were compared with the other two surgical groups (3D fabric disc alone; 3D fabric disc with additional anterior instrumentation stabilization). The 3D fabric disc and HA/PLLA-spinal segments demonstrated segmental mobility at 15 and 24 months; however, the range of motion (ROM) in flexion-extension decreased to 49 and 40%, respectively, despite statistically equivalent preserved torsional ROM. Histologically there was excellent osseous fusion at the 3D fabric disc surface-vertebral body interface. At 2 years posttreatment, no adverse tissue reaction nor aseptic loosening of the device was observed. CONCLUSIONS: Intervertebral disc replacement with the 3D fabric disc was viable and when used in conjunction with the bioresorbable HA/PLLA spinal augmentation. Further refinements of device design to create a stand-alone type are necessary to obviate the need for additional spinal stabilization., American Association of Neurological Surgeons, English
• 脊髄損傷治療に対する免疫学的アプローチ
  角家健; 三浪明男; 永野裕介; 今重之; 上出利光, 日本整形外科学会雑誌, 78, 8, 2004
• Effectiveness of transforaminal endoscopic surgery for pyogenic spondylodiscitis
  ITO M., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 14, 1, 156, 156, 20 Feb. 2003
  Japanese
• Correction of postlaminectomy kyphosis using cervical pedicle screw fixation system
  KADOYA K., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 14, 1, 105, 105, 20 Feb. 2003
  Japanese
• Efficacy of computer-assisted surgery in the treatment of cervical disorders
  KOTANI Y., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 14, 1, 10, 10, 20 Feb. 2003
  Japanese
• Lumbar disc herniation associated with the separation of ring apophysis : Is removal of detached apophysis mandatory to achieve a satisfactory result?
  SHIRADO O., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 14, 1, 47, 47, 20 Feb. 2003
  Japanese
• Complications of cervical pedicle screw fixation in reconstructive surgery in the cervical spine
  ABUMI K., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 14, 1, 307, 307, 20 Feb. 2003
  Japanese
• Artificial intervertebral disc replacement using supplemental bioabsorbable spinal fixation : 2year experimental results and future starategy
  KOTANI Y., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 13, 1, 7, 7, 26 Apr. 2002
  Japanese
• Bioabsorbable spianl fixation using high strength hydroxyappatite/poly-L-lactide composite
  KADOYA K., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 12, 1, 288, 288, 27 Apr. 2001
  Japanese
• Risk factor analysis for osteoporotic vertebral collapse
  TANEICHI H., 日本脊椎脊髄病学会雑誌 = The journal of the Japan Spine Research Society, 12, 1, 215, 215, 27 Apr. 2001
  Japanese
• Biomechanical evaluation of anterior spinal instrumentation for scoliosis : In vitro fatigue simulation of screw loosening mechanism
  SHIMAMOTO Norimichi, 日本臨床バイオメカニクス学会誌 = Proceedings of ... Annual Meeting of Japanese Society for Clinical Biomechanics and Related Research, 21, 27, 32, 01 Oct. 2000
  Japanese
• Viscoelastic and fatigue properties of sheep artificial intervertebral disc
  KADOYA Ken, 日本臨床バイオメカニクス学会誌 = Proceedings of ... Annual Meeting of Japanese Society for Clinical Biomechanics and Related Research, 21, 49, 52, 01 Oct. 2000
  Japanese
• Evaluation of Bonding Strength between Bone and Artificial Intervertebral Disc Using Three-dimensional Fabric
  TAKAHATA M., 日本整形外科學會雜誌, 74, 8, S1530, 25 Aug. 2000
  Japanese
• Histomorphometric Analysis of the Bone Ingrowth between Bone and Artificial Intervertebral Disc in Sheep
  MATSUMOTO S., 日本整形外科學會雜誌, 74, 8, S1531, 25 Aug. 2000
  Japanese
• Spinal Bioresorbable Fixation Using Ultra-high-strength Hydroxyapatite/poly (L-lactide) Composites
  KADOYA K., 日本整形外科學會雜誌, 74, 8, S1651, 25 Aug. 2000
  Japanese
• Vertebral Body Repla Cement Using a Porous-surfaced Apatite-wollastonite Glass Ceramic Prosthesis in a Sheep Model. A Histologic study
  TAKADA T., 日本整形外科學會雜誌, 74, 8, S1818, 25 Aug. 2000
  Japanese
• Development of Total Artificial Intervertebral Disc and Its Consideration on Clinical Application
  KOTANI Y., 日本整形外科學會雜誌, 74, 8, S1335, 25 Aug. 2000
  Japanese
• Vertebral body replacement using a porous-surfaced apatite-wollastonite glass ceramic prosthesis in a sheep model.
  TAKADA T., 日本脊椎外科学会雑誌 = The journal of the Japan Spine Research Society, 11, 1, 82, 82, 28 Apr. 2000
  Japanese
• Total artificial disc replacement using bioabsorbable spinal fixation device
  KOTANI Y., 日本脊椎外科学会雑誌 = The journal of the Japan Spine Research Society, 11, 1, 120, 120, 28 Apr. 2000
  Japanese
• The Use of Bioabsorbable Spinal Fixation for Total Intervertebral Disc Replacement
  KOTANI Y., 日本整形外科學會雜誌, 74, 2, S138, 25 Feb. 2000
  Japanese
• Biomechanical and Histologic Analysis of Total Intervertebral Disc Replacement using Multiaxial Three-dimensional Fabrics
  KOTANI Yoshihisa, 日本臨床バイオメカニクス学会誌 = Proceedings of ... Annual Meeting of Japanese Society for Clinical Biomechanics and Related Research, 20, 13, 18, 01 Oct. 1999
  Japanese
• Biomechanical property of sheep artificial intervertebral disc using three-dimensional fabric and its alteration in vivo
  KADOYA Ken, 日本臨床バイオメカニクス学会誌 = Proceedings of ... Annual Meeting of Japanese Society for Clinical Biomechanics and Related Research, 20, 1, 6, 01 Oct. 1999
  Japanese
• 人工椎間板の開発に関する生体力学的・組織学的研究(第2報)
  小谷 善久; 金田 清志; 鐙 邦芳; 高田 宇重; 角家 健; 島本 則道; 海老原 響; 松本 聡子; 敷波 保夫; 廉澤 剛, 日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association, 73, 8, S1934, 25 Aug. 1999
  Japanese
• Viscoelastic and fatigue biomechanical properties of sheep artificial intervertebral disc using three-dimensional fabrics
  KADOYA K., 日本脊椎外科学会雑誌 = The journal of the Japan Spine Research Society, 10, 1, 173, 173, 26 Apr. 1999
  Japanese
• Tensile-compresive and torsional biomechanical properties of sheep artificial intervertebral disc and their alterations in vivo
  KADOYA K., 日本脊椎外科学会雑誌 = The journal of the Japan Spine Research Society, 10, 1, 172, 172, 26 Apr. 1999
  Japanese
• The development of total artificial intervertebral disc and its prospects for clinical application
  KOTANI Y., 日本脊椎外科学会雑誌 = The journal of the Japan Spine Research Society, 10, 1, 104, 104, 26 Apr. 1999
  Japanese
• 全置換型人工椎間板の開発と臨床応用の展望
  小谷 善久; 金田 清志; 鐙 邦芳; 高田 宇重; 敷波 保夫; 角家 健; 島本 則道; 廉澤 剛, 日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association, 73, 2, S152, 25 Feb. 1999
  Japanese
• Surgical treatment of avulsion fracture of the tibial attachment of the posterior cruciate ligament - First report: Posterior instability of the knee
  E. Kondo; M. Inoue; M. Saita; T. Ohya; N. Iwasaki; H. Watanabe; K. Kadoya; N. Shimamoto, Hokkaido Journal of Orthopaedics and Traumatology, 41, 25, 29, 01 Dec. 1998
• 後十字靱帯脛骨付着部裂離骨折の手術治療(第一報) 特に後方動揺性について
  近藤 英司; 井上 雅之; 斉田 通則; 大矢 卓; 岩崎 倫政; 渡辺 裕樹; 角家 健; 島本 則道, 北海道整形災害外科学会雑誌, 41, 1, 25, 29, Nov. 1998
  対象は過去3年間に手術治療を要した9人9膝で,年齢は平均50歳,経過観察期間は平均16ヵ月であった.手術適応は裂離骨片の大きさが1cm以上で,後十字靱帯脛骨付着部より2mm以上転位しているものとした.手術は膝窩部を展開し裂離骨片を整復後,螺子固定を行った.術後,X線学的には全例整復位での骨癒合が得られていた.Lysholm knee scoring scaleは平均95点で,関節可動域は屈曲平均145度であった.sagging,後方引き出し試験が陽性であるものは9膝中5膝.Knee Laxity Tester(Stryker Co.USA)でのanteriorposterior total knee laxityは対健側差+2.7±1.6(平均±標準偏差)mmであり,5膝に3〜5.7mmの対健側差を認めた, 北海道整形災害外科学会, Japanese
• Biomechanical Property of the Sheep Artificial Intervertebral Disc and its Morphological Alteration in vivo
  KADOYA K., 日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association, 72, 8, S1418, 25 Aug. 1998
  Japanese
• Biomechanical and Histological Study on the Development of Artificial Intervertebral Disc Prosthesis
  KOTANI Y., 日本整形外科學會雜誌 = The Journal of the Japanese Orthopaedic Association, 72, 8, S1416, 25 Aug. 1998
  Japanese

• 基本医学総論, 2024年, 修士課程, 医学院
• 基本医学研究, 2024年, 修士課程, 医学院
• 医学総論, 2024年, 博士後期課程, 医学研究科
• 基本医学総論, 2024年, 修士課程, 医学院
• 医学総論, 2024年, 博士後期課程, 医学院
• 臨床医学概論, 2024年, 修士課程, 医学院
• 医学総論, 2024年, 博士後期課程, 医学院
• 基盤医学研究, 2024年, 博士後期課程, 医学院
• 臨床医学研究, 2024年, 博士後期課程, 医学院

• Elucidation of peripheral nerve axon regeneration mechanism mediated by Schwann cells
  Grants-in-Aid for Scientific Research
  01 Apr. 2024 - 31 Mar. 2027
  角家 健
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 24K02348
• 好中球細胞外トラップを標的とした末梢神経再生方法の開発
  科学研究費助成事業
  01 Apr. 2023 - 31 Mar. 2026
  河村 太介; 角家 健; 遠藤 健
  末梢神経は再生するが、重度損傷、近位部損傷、再建例の成績は必ずしも良好ではなく、現在行われている治療も、半世紀以上前と大きくは変わらず、より効果的な治療方法開発への社会的要請は大きい。申請者らは、末梢神経のワーラー変性部では、好中球が神経上膜に集積し、好中球細胞外トラップ（Neutrophil extracellular traps：NETs)を分泌することで、神経実質内へのマクロファージ集積を遅延し、損傷神経の修復機転を阻害していることを同定した。本研究では、この知見をさらに発展させ、神経上膜のNETsは末梢神経の治療標的であるという仮説を検証する。まず、末梢神経損傷の形態の違いによるNETs発現パターンを明らかにした。その結果、その結果、損傷、再建方法に関わらず、ワーラー変性部の神経上膜には、損傷12時間後をピークとする好中球の集積とNETsの発現を認めた。本結果は、好中球がワーラー変性部の神経上膜に集積し、好中球細胞外トラップの分泌を介する現象の普遍性を示している。続いて、NETs阻害が末梢神経損傷後の機能再生を促進するか検討した。圧挫損傷後に2時間だけ、ワーラー変性部の神経表面をNETs阻害薬（DNase)含有コラーゲンシートで被覆し、7日目に組織評価を実施したところ、１週後のデブリスの減少と軸索再生促進効果を認めた。さらに、圧挫損傷後にIgGの腹腔内投与を行い、12時間後のNETs阻害効果と、6週間後の感覚機能、歩行機能、電気生理機能を検討した結果、NETsの発現は有意に阻害され、最終的な感覚機能、歩行機能、潜時と振幅が有意に改善した。最後に、中枢神経のワーラー変性部でもNETsが発現するか、マウス脊髄損傷モデルを使用して検討した。その結果、脊髄のワーラー変性部では末梢神経と異なり、好中球の集積とNETsの発現を認めなかった。
  日本学術振興会, 基盤研究(C), 北海道大学, 23K08602
• 移植組織制御による新規脊髄再生方法の開発
  科学研究費助成事業 基盤研究(B)
  01 Apr. 2020 - 31 Mar. 2023
  角家 健
  神経前駆細胞移植によって、脊髄損傷部を新しい神経組織で充たすことが可能になったが、正常組織と異なり、移植組織内の神経細胞の位置は全くの無秩序である。神経前駆細胞移植による機能再生効果を向上させるためには、秩序だった神経細胞の配置が重要であると予想されるが、未だ、移植神経細胞の位置を制御する方法は開発されていない。発生期では、神経前駆細胞がモルフォゲンの濃度勾配を位置情報として利用することで、脊髄組織の構成にパターンを形成する。そこで、本研究の目的は、脊髄損傷部に移植された神経前駆細胞はモルフォゲンの濃度勾配を位置情報として利用できるという仮説を検討することである。これまでに、マウスの５種類のモルフォゲン（BMP4、Wnt1、Sonic Hedge Hog、Netrin1、Draxin)のクローニングを完了し、第３世代のレンチウイルスによる、線維芽細胞への遺伝子導入システムを確立、各モルフォゲンとコントロールの計６種類のレンチウイルスを作成し、FACSを使用して、５種類のモルフォゲンを分泌する同系マウス由来の線維芽細胞の作成を完了した。また、これらの線維芽細胞の脊髄への移植方法と、胚性脊髄由来の神経前駆細胞を損傷部に移植し、新規神経組織の作成方法も確立した。最後に、免疫染色によって、移植神経細胞のパターン形成評価方法も確立した。
  日本学術振興会, 基盤研究(B), 北海道大学, 20H03558
• VCP化合物の最適化による新規神経保護薬の開発
  科学研究費助成事業 基盤研究(C)
  01 Apr. 2020 - 31 Mar. 2023
  船木 智; 中川 慎介; 角家 健; 周東 智
  脊髄損傷に対する有効な治療法はいまだ確立されておらず、その治療法の確立が求められている。これまでの研究から、一次損傷に引き続いておこる、血液脳脊髄関門の破綻を防ぐことで、二次損傷を軽減できる可能性が示されているが、その具体的な方法はいまだ確立されてない。本研究では、約2400の北海道大学独自の化合物をスクリーニングした結果、類似の化合物の類縁体１４剤が培養ヒト脳血管内皮細胞に対する細胞保護作用を持つことを見出した。そこで、本研究の目的は、これらの化合物の応用により、脳脊髄血管内皮細胞保護作用を介して、血液脳脊髄関門の破綻を防ぎ、脊髄損傷後の二次損傷を軽減することで、最終的に神経保護作用を発揮する新規神経保護薬を開発することである。本年度は、代表的なVCP化合物を大量に作成し、正常マウス、および脊髄損傷マウスに腹腔内投与して、経時的血液濃度を測定した。その結果、培養脳血管内皮細胞に有効であった濃度と同様の血中濃度が腹腔内投与でも得られること、VCP化合物の投与によって明らかな副作用を生じないこと、VCP化合物の腹腔内投与によってマウス脊髄損傷後のIgG漏出面積を抑制することを確認した。このことは、VCP化合物が、腹腔内投与で動物実験に使用可能なほど安全で、脊髄損傷後の血液脊髄関門機能の破綻を抑制することを示している。現在、VCP化合物による脊髄損傷後の組織保護効果、機能保護効果を検討中である。
  日本学術振興会, 基盤研究(C), 北海道大学, 20K09449
• Investigation of gait parameters obtained by wearable device and modifying factors affecting cognitive function in the elderly
  Grants-in-Aid for Scientific Research
  01 Apr. 2020 - 31 Mar. 2022
  Tamakoshi Akiko
  To lead an independent life, it is fundamental to be able to move where one wants by oneself, that is, to be able to walk. In this study, we investigated the relationship between gait parameters and cognitive function measured by MoCA-J for 70-79 year olds living in 6 towns in Hokkaido, Japan, who were not certified as caregivers. A non-invasive, easy-to-measure wearable device was used to ascertain gait parameters, and the relationship with cognitive function measured by the MoCA-J was investigated. From a survey conducted in 2018 with 236 participants, we statistically analysed the 20 gait parameters obtained and extracted four gait factors (general cycle, initial contact, propulsion, and mid-swing). In both the cross-sectional study (cognitive function in 2018) and the follow-up study (cognitive function in 2021, 165 participants), better general cycle was found to be associated with higher cognitive function.
  Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Research (Pioneering), Hokkaido University, 20K20395
• Study of the cellular and cell adhesion molecule mechanisms underlying peripheral nerve axon regeneration
  革新的先端研究開発支援事業プライム
  Oct. 2018 - Mar. 2022
  AMED, プライム, Principal investigator, 20gm6210004h0003
• Development of a novel neuroprotection drug for spinal cord injury
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2017 - 31 Mar. 2020
  Asano Tsuyoshi
  The current study has developed a high-throughput screening assay (HTSA) for identifying drugs to protect the blood brain spinal cord barrier (BBSCB) function. Actual screening of FDA approved drugs by this HTSA identified Berberine as a potential drug to protect BBSCB. Berberine protected BBSCB functions from oxygen-glucose deprivation and reoxygenation stress in vitro coculture model as well as cervical spinal cord injury (SCI) and traumatic brain injury models. Furthermore, Berberine reduced lesion size and neuronal loss and improved gait performances after cervical SCI in mice. The current study established the useful HTSA to find potential neuroprotective drugs by maintaining BBSCB functions and identified Berberine as a novel BBSCB protection drug.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K10913
• Identification of optimum Schwann cell for peripheral nerve regeneration
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2017 - 31 Mar. 2020
  Kawamura Daisuke
  The current project has developed a new experimental model, which can elucidate the axon-promoting effects of grafted cells. It succeeded in clearly demonstrating that the graft of Schwann cells (SCs) but not marrow stromal cells or fibroblasts promoted axonal growth. In addition, this model demonstrated that there was a linear relationship of the SC amount with the extent of axon regeneration. Then, we tested four types of SCs (SC precursors (SCPs), immature SCs (ISCs), repair SCs (RSCs), and non-RSCs) using this model. RSCs had the greatest axon regeneration, and non-RSCs was the next. But, SCPs and ISCs failed to support axon regeneration. Further, in vitro co-culture of dorsal root ganglion (DRG) neurons, transcriptome, and quantification of neurotrophic factor productions also support this finding. These findings indicate that peripheral axon regeneration depends on types of SCs, contributing to the development of a novel therapy for peripheral nerve injury.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K10914
• New neural circuit formation in chronically injured spinal cord by neural stem cell grafts
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2017 - 31 Mar. 2020
  Kadoya Ken
  In this study, we investigated the potential of transplantation of neural stem cells at the chronic stage of spinal cord injury by comparing to sub-acute transplantation. Transplanted neural stem cells survived well in chronic lesion sites and generated many neurons. These neurons extended axons in host spinal cords in high numbers for long distances and connected to host neurons below injury. There was no significant difference of the number of extending axons between chronically and sub-acutely transplanted subjects. Further, chronically injured corticospinal tract axons regenerated into neural stem cells, though its extent was less robust than sub-acute transplantation. These findings indicate that early stage neural cells have a remarkable ability to extend axons over inhibitory environment at the chronic stage of spinal cord injury.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K10915
• Development of novel therapy for peripheral nerve regeneration by combinatorial cell therapy
  Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
  01 Apr. 2017 - 31 Mar. 2020
  Nagano Yusuke
  The objectives of the current study are to investigate spatiotemporal distribution of macrophage subtypes after peripheral nerve injury and to clarify their axon-promoting effects. Immunolabeling study in rat sciatic nerve crush injury demonstrated that the distribution pattern of M2 but not M1 macrophage was similar to that of regenerating axons in injured peripheral nerve. The graft of M2 but not M1 macrophage promoted axon regeneration. Further, the graft of M2 macrophage had partial effect on motor and sensory recovery after peripheral nerve injury. Elucidation of the molecular and cellular mechanisms of the effect of M2 macrophage on axon regeneration might lead to the new therapeutic strategy for peripheral nerve injury.
  Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 17K11527
• Identification of regeneration associated gene of central nervous system: axon regeneration of corticospinal tract
  Grants-in-Aid for Scientific Research Grant-in-Aid for Research Activity Start-up
  28 Aug. 2015 - 31 Mar. 2017
  KADOYA KEN; Gibbs Daniel; Tuszynski Mark; Stobl Hans; ENDO Takeshi
  Regeneration associated genes are identified in peripheral but not central nervous system. The purpose of the current study is to determine whether transcription factor cJun is the regeneration associated gene of central nervous system. cJun expressions were manipulated in the experimental model, in which corticospinal tract axons regenerated into grafted cells. Regulation of cJun did not affect the extent of regeneration of corticospinal axons at all, indicating that cJun is not the regeneration associated gene of corticospinal axons and that the central nervous system does not share the mechanism of regeneration with peripheral nervous system.
  Japan Society for the Promotion of Science, Grant-in-Aid for Research Activity Start-up, Hokkaido University, 15H05989

• 脊髄誘発電位測定用電極および脊髄誘発電位測定装置
  Patent right, 及川 陽一; 古川 博之; 角家 健; 永野 裕介, 富士通株式会社, 国立大学法人 北海道大学
  特願2004-381997, 28 Dec. 2004
  特開2006-187342, 20 Jul. 2006
  200903075038255563
• 神経突起伸長促進剤及び神経再生誘導用医薬組成物
  Patent right, 角家健; 鈴木智亮
  特願2021-160064
• 末梢神経損傷の治療のための医薬組成物
  Patent right, 角家健; 山本康弘
  特願2021-126207
• ＧＦＲα１を含む神経突起伸長促進剤及び神経再生誘導用医療材料
  Patent right, 角家健; 鈴木智亮; 遠藤健
  特願2020- 218091
• 血液脳脊髄関門保護剤
  Patent right, 角家健、鈴木裕貴、五月女慧人、前仲勝実、乙黒聡子
  特願2020-109190
• 破骨細胞分化抑制剤
  Patent right, テルカウイ モハマド; アラー; ハッサン シエーク; 角家健; 高橋大介; 岩崎倫政
  特願1. 2018-148040