Researcher Profile and Settings

Affiliation

• Faculty of Health Sciences　Health Sciences　Department of Rehabilitation Science

Job Title

• Assistant Professor

Research funding number

• 10965354

ORCID ID

•  https://orcid.org/0000-0002-9107-6320

J-Global ID

• 202201005653422817

Research Interests

• 関節軟骨、変形性関節症、運動療法、理学療法、リハビリテーション   

Research Areas

• Life sciences / Rehabilitation science / osteoarthritis exercise

Education

• 2022/04 - 2023/03  Saitama Prefectural University  Graduate Course of Health and Social Services
• 2019/04 - 2022/03  Saitama Prefectural University  Graduate Course of Health and Social Services
• 2017/04 - 2019/03  Saitama Prefectural University  Graduate Course of Health and Social Services
• 2013/04 - 2017/03  Saitama Prefectural University  School of Health and Social Services  Department of Physical Therapy

Research Activities

Published Papers

• Chronic Ankle Joint Instability Induces Ankle Sensorimotor Dysfunction: A Controlled Laboratory Study

  Sora Kawabata, Kaichi Ozone, Yuki Minegishi, Yuichiro Oka, Hidenobu Terada, Chiharu Takasu, Takuma Kojima, Takuma Kano, Naohiko Kanemura, Kenji Murata

  The American Journal of Sports Medicine 0363-5465 2024/01/27 

  Background: Chronic ankle instability (CAI) is a clinical sequela that causes the recurrence of ankle sprain by inducing ankle sensorimotor dysfunction. Animal models of CAI have recently shown that ankle ligament injuries mimicking an ankle sprain result in chronic loss of ankle sensorimotor function. However, the underlying mechanisms determining the pathogenesis of CAI remain unclear. Hypothesis: Ankle instability after an ankle sprain leads to the degeneration of the mechanoreceptors, resulting in ankle sensorimotor dysfunction and the development of CAI. Study Design: Controlled laboratory study. Methods: Four-week-old male Wistar rats (N = 30) were divided into 2 groups: (1) the ankle joint instability (AJI) group with ankle instability induced by transecting the calcaneofibular ligament (n = 15) and (2) the sham group (n = 15). Ankle instability was assessed using the anterior drawer test and the talar tilt test at 4, 6, and 8 weeks after the operation (n = 5, for each group at each time point), and ankle sensorimotor function was assessed using behavioral tests, including ladder walking and balance beam tests, every 2 weeks during the postoperative period. Morphology and number of mechanoreceptors in the intact anterior talofibular ligament (ATFL) were histologically analyzed by immunofluorescence staining targeting the neurofilament medium chain and S100 proteins at 4, 6, and 8 weeks postoperatively (n = 5 per group). Sensory neurons that form mechanoreceptors were histologically analyzed using immunofluorescence staining targeting the mechanosensitive ion channel PIEZO2 at 8 weeks postoperatively (n = 5). Results: Ankle sensorimotor function decreased over time in the AJI group, exhibiting decreased ankle instability compared with the sham group ( P = .045). The number of mechanoreceptors in the ATFL was reduced ( P < .001) and PIEZO2 expression in the sensory neurons decreased ( P = .008) at 8 weeks postoperatively. The number of mechanoreceptors was negatively correlated with ankle sensorimotor dysfunction ( P < .001). Conclusion: The AJI model demonstrated degeneration of the mechanoreceptors in the ATFL and decreased mechanosensitivity of the sensory neurons, which may contribute to CAI. Clinical Relevance: Ankle instability causes degeneration of mechanoreceptors and decreases the mechanosensitivity of sensory neurons involved in the development of CAI. This finding emphasizes the importance of controlling ankle instability after ankle sprains to prevent recurrence and the onset of CAI.
• The infrapatellar fat pad contributes to spontaneous healing after complete anterior cruciate ligament injury.

  Takuma Kano, Yuki Minegish, Hidenobu Terada, Chiharu Takasu, Takuma Kojima, Yuichiro Oka, Sora Kawabata, Naoki Shimada, Yuri Morishita, Kenji Murata, Naohiko Kanemura

  Experimental biology and medicine (Maywood, N.J.) 248 (20) 1895 - 1904 2023/10 

  Anterior cruciate ligament (ACL) injuries have a very low healing capacity but have recently been shown to heal spontaneously with conservative treatment. This study examined the mechanism of spontaneous ACL healing by focusing on the intra-articular tissues of the knee joint. Skeletally mature Wistar rats (n = 70) were randomly assigned to two groups: the controlled abnormal movement (CAM) and anterior cruciate ligament transection (ACLT) groups. The ACL was completely transected at the mid-portion in both groups. Only the CAM group underwent extra-articular braking to control for abnormal tibial translation. The animals were allowed full cage activity until sacrifice for histological, and molecular biology analyses. The results showed that the behavior of the stump after ACL injury differed between models 12 h after injury. The femoral stump in the ACLT group retreated posteriorly and upwardly. Macrophage polarity analysis revealed that the stump immune response in the CAM group was more activated than that in the ACLT group 6 h after injury. Microarray analysis of the ACL parenchyma and infrapatellar fat pads suggested the involvement of nuclear factor kappa B (NF-κB) signaling. Real-time polymerase chain reaction (PCR) analysis showed that NF-κB gene expression in the infrapatellar fat pad was significantly increased in the CAM group than in the ACLT group. However, there was no difference in the gene expression levels in the ACL parenchyma between models. In conclusion, the healing response of the ACL was activated within 12 h of injury, resulting in differences in the healing response between the models. It has been suggested that infrapatellar fat pads are involved in the healing process and that angiogenesis and antiapoptotic effects through NF-κB signaling may contribute to this mechanism.
• 特集 運動器理学療法をどう捉えるか-統合的戦略で自らの思考の枠を乗り越える メカニカルストレスと理学療法

  金村 尚彦, 久保田 圭祐, 加納 拓馬, 森下 佑里, 岡 優一郎, 小曽根 海知, 峯岸 雄基, 村田 健児

  理学療法ジャーナル 株式会社医学書院 57 (9) 1057 - 1063 0915-0552 2023/09/15
• Mild treadmill exercise inhibits cartilage degeneration via macrophages in an osteoarthritis mouse model

  Yuichiro Oka, Kenji Murata, Kaichi Ozone, Yuki Minegishi, Takuma Kano, Naoki Shimada, Naohiko Kanemura

  Osteoarthritis and Cartilage Open 5 (2) 100359 - 100359 2665-9131 2023/04
• Biochemical reactions between intra-articular tissues and joint instability in a rat model of osteoarthritis

  Kenji Murata, Sora Kawabata, Takuma Kojima, Yuichiro Oka, Chiharu Takasu, Hidenobu Terada, Naohiko Kanemura

  2023/03/29 

  Abstract Aims Joint instability is associated with various joint conditions including osteoarthritis (OA) and inflammation, and we have developed model which is determined to role of knee instability. Investigating cartilage maintenance factors such as hyaluronic acid (HA) and glycosaminoglycans (GAGs) can provide insights into the effect of the mechanical stress and the inhibitor used, with the following aims: 1) whether cartilage degeneration is inhibited in the new model, 2) whether combination TGF-β1 inhibition mitigates cartilage degeneration, and to determine the role of TGF-β1 in synovitis using fibroblasts. Main methods We used this novel model to investigate inhibition of OA progression with a focus on HA and GAGs, which help maintain the cartilage and synovial membrane. In detail, mechanical tests, X-ray, histological, and protein and mRNA expression analyses were used to determine the role of joint stability using in vivo model or fibroblast from synovial membrane. Key findings Joint stability mitigated cartilage degeneration loss, decreased osteophytes, increased the expression levels of HA and GAGs in the synovial membrane, and decreased the release of pro-inflammatory factors in rats. Moreover, injection of TGF-β1 inhibitor in an inflammatory synovial membrane promoted HA and GAGs expression. In synovial fibroblast cells, inhibition of TGF-β1 over expression significantly inhibited the downregulation of pro-inflammatory factors and promoted the upregulation of lubrification for cartilage. Significance Our results suggest that joint instability is an independent mechanical factor for OA progression. The results provide novel insights into the association between OA and joint instability, which has significant human sciences implications. Research Highlights • Established a new experimental rat model of the different joint instability for elucidate osteoarthritis onset/progression • Using Histological staining to investigated the osteoarthritis including synovitis and osteophytes of the novel model • Using fibroblast from synovial membrane to investigated the fibrosis • Joint instability exacerbates articular cartilage degeneration and decreases HA and GAGs protein expressions in synovial membrane • TGF-β1 inhibitor on early osteoarthritis joints may suppress synovial inflammation
• The Effects of Downhill Running and Maturation on Histological and Morphological Properties of Tendon and Enthesis in Mice.

  Kaichi Ozone, Yuki Minegishi, Yuichiro Oka, Michiaki Sato, Naohiko Kanemura

  Biology 12 (3) 2023/03/16 

  To date, it remains unclear how overuse affects the tendons and entheses at different stages of maturation. Therefore, we evaluated histological and morphological changes in the tendons and entheses in adolescent (4-week-old) and adult mice (8-week-old) by performing flat-land and downhill running exercises. The mice were divided into the Sedentary, High Flat (flat-land high-speed running; concentric-contraction exercise), Low Down (downhill low-speed running; eccentric-contraction exercise), and High Down (downhill high-speed running; eccentric-contraction exercise) groups. Histological changes and inflammatory factor expressions were compared in the entheses and tendons after 4 weeks of exercise. Downhill, but not flat-land high-speed running, induced muscle-tendon complex hypertrophy in both adolescent and adult mice. Histological enthesis changes were induced in both groups during downhill running but were less pronounced in adult mice. Conversely, no significant cell aggregation or fiber orientation changes were observed in the tendon, but increased inflammatory factors were observed in both groups, with significantly higher expression in the tendons of adult mice. Downhill running induced histological and morphological enthesis changes and inflammatory factor increase in the tendons, regardless of running speed variations. These results may help elucidate the pathogenesis of enthesopathy and tendinopathy, which have different pathophysiologies despite having the same pathogenetic factors.
• Eccentric contraction-dominant exercise leads to molecular biological changes in enthesis and enthesopathy-like morphological changes.

  Kaichi Ozone, Yuki Minegishi, Kei Takahata, Haruna Takahashi, Moe Yoneno, Shinya Hattori, Li Xianglan, Yuichiro Oka, Kenji Murata, Naohiko Kanemura

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 2022/06/18 [Refereed]
   

  Entheses, which are tendon-to-bone attachment sites in the musculoskeletal system, play important roles in optimizing the mechanical stress and force transmitted from the muscle to the bone. Sports-related enthesopathy shows pathological features, including hyperplasia of the fibrocartilage (FC) region in the enthesis. The amount of exercise and type of muscle contraction during movement is involved in the pathogenesis of sports-related enthesopathy; however, the details of this condition are unclear. Here we examined the molecular pathways involved in the morphological changes of the muscle-tendon-enthesis complex and enthesis FC region in the supraspinatus muscle enthesis of mice under different exercise conditions. Following intervention, morphological changes in the muscle-tendon-enthesis complex were initiated in the eccentric contraction-dominant exercise group at 2 weeks, with activation of the transforming growth factor-β (TGFβ) superfamily pathway predicted by proteome and ingenuity pathway analyses. Histological and molecular biological analyses confirmed the activation of the TGFβ/bone morphogenetic protein (BMP)-Smad pathway. The concentric contraction-dominant exercise group showed no change in the morphology of the muscle-tendon-enthesis complex or activation of the TGFβ/BMP-Smad pathway, despite overuse exercise. Statement of Clinical Significance: These results suggest that eccentric contraction-dominant exercise induces sports-related enthesopathy-like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor-β superfamily pathway in enthesis. Statement of Clinical Significance: These results suggest that eccentric contraction-dominant exercise induces sports-related enthesopathy-like morphological changes in the early stages as well as molecular biological changes, mainly in the transforming growth factor-β superfamily pathway in enthesis.
• Effects of exercise on muscle reinnervation and plasticity of spinal circuits in rat sciatic nerve crush injury models with different numbers of crushes.

  Yuki Minegishi, Junji Nishimoto, Minori Uto, Kaichi Ozone, Yuichiro Oka, Takanori Kokubun, Kenji Murata, Hidenori Takemoto, Naohiko Kanemura

  Muscle & nerve 65 (5) 612 - 620 2022/05 [Refereed]
   

  INTRODUCTION/AIMS: Motor function recovery is frequently poor after peripheral nerve injury. The effect of different numbers of nerve crushes and exercise on motor function recovery is unknown. We aimed to examine how different numbers of crushes of the rat sciatic nerve affects muscle reinnervation and plasticity of spinal circuits and the effect of exercise intervention. METHODS: Single and multiple sciatic nerve crush models with different numbers of crushes were created in rats. Treadmill exercise was performed at 10 m/min for 60 min, five times a week. Muscle reinnervation and synaptic changes in L4-5 motor neurons were examined by immunofluorescence staining. Behavioral tests were the sciatic functional index (SFI) and the pinprick tests. RESULTS: The percentage of soleus muscle reinnervation was not significantly increased by the presence of exercise in single or multiple crushes. Exercise after a single crush increased the contact of motor neurons with VGLUT1-containing structures (Exercised vs. Unexercised, 12.9% vs. 8.7%; p < .01), but after multiple crushes, it decreased with or without exercise (8.1% vs. 8.6%). Exercise after a single crush significantly improved SFI values from 14 to 24 days, and exercise after multiple crushes from 21 to 35 days (all p < .05). The pinprick test showed no difference in recovery depending on the number of crushes or whether or not exercised. DISCUSSION: Different numbers of sciatic nerve crushes affect muscle reinnervation and motor neuron synaptic changes differently, but motor function recovery may improve with exercise regardless of the number of crushes.
• The difference in joint instability affects the onset of cartilage degeneration or subchondral bone changes

  Arakawa K, Takahata K, Enomoto S, Oka Y, Ozone K, Nakagaki S, Murata K, Kanemura N, Kokubun T

  Osteoarthritis Cartilage . 2022. 30(3): 451-460. 30 (3) 451 - 460 1063-4584 2022/03 [Refereed]
   

  Objective: It has been debated whether the onset of knee osteoarthritis is initiated in cartilage or subchondral bone. The purpose of this study was to clarify the effects of increasing or decreasing joint instability on cartilage degeneration and subchondral bone changes in knee OA by comparing different models of joint instability. Design: We used the anterior cruciate ligament transection (ACL-T) model and the destabilization of the medial meniscus (DMM) model. In addition, we created a controlled abnormal tibial translation (CATT) model and a controlled abnormal tibial rotation (CATR) model. We performed joint instability analysis, micro computed tomography analysis, histological and immunohistological analysis in 4 and 6 weeks. Results: The CATT group suppressed joint instability in the ACL-T group (6 weeks; p = 0.032), and the CATR group suppressed joint instability in the DMM group (6 weeks; p = 0.032). Chondrocyte hypertrophy in the ACL-T and DMM groups was increased compared to the Sham group (6 weeks; [ACL-T vs Sham], p=0.002, 95%CI [5.983 - 33.025]; [DMM vs Sham], p=0.022, 95%CI [1.691 - 28.733]). In the subchondral bone, the BV/TV in the DMM and CATR groups was increased compared to the ACL-T and CATT groups (6 weeks; [DMM vs ACL-T], p=0.002, 95%CI [7.404 - 37.582]; [DMM vs CATT], p=0.014, 95%CI [2.881 - 33.059]; [CATR vs ACL-T], p=0.006, 95%CI [4.615 - 34.793]; [CATR vs CATT], p=0.048, 95%CI [0.092 - 30.270]). Conclusions: This study showed that joint instability promotes chondrocyte hypertrophy, but subchondral bone changes were influenced by differences in ACL and meniscus function. Keywords: joint instability; osteoarthritis; pathogenesis.
• Influence of the site of injury on the spontaneous healing response in a rat model of total rupture of the anterior cruciate ligament.

  Takuma Kano, Takanori Kokubun, Kenji Murata, Yuichiro Oka, Kaichi Ozone, Kohei Arakawa, Yuri Morishita, Kiyomi Takayanagi, Naohiko Kanemura

  Connective tissue research 63 (2) 138 - 150 2022/03 [Refereed]
   

  AIM: The healing ability of the anterior cruciate ligament (ACL) injury is very poor; however, it has recently been shown to undergo self-healing with conservative treatments. In this study, we evaluated the influence of the site of injury on the healing process after complete transverse tear of ACL using a rat model. MATERIALS AND METHODS: A total of 58 skeletally mature Wistar rats were randomly assigned to various ACL injury groups: controlled abnormal movement-mid-portion (CAM-MP), controlled abnormal movement-femoral side (CAM-FS), ACL transection-mid-portion (ACLT-MP), or ACL transection-femoral side (ACLT-FS) injury groups. The ACL was completely transected in the mid-portion in the ACLT-MP and CAM-MP groups, and on the femoral side in the ACLT-FS and CAM-FS groups. Both CAM groups underwent extra-articular braking to control for abnormal tibial translation. The animals were allowed full cage activity until sacrifice postoperatively for histological and biomechanical assessment. RESULTS: Significant differences were found in the ratios of residual ligament lengths between the CAM-MP and CAM-FS groups, demonstrating the validity of each model. Spontaneous healing of the injured ACL was observed in the CAM-MP and CAM-FS groups but not in the ACLT-MP and ACLT-FS groups. The mechanical strength of the healing ACL did not differ between the CAM-MP and CAM-FS groups 8 weeks after injury; however, the former had better mechanical strength than the latter 12 weeks after the injury. CONCLUSION: ACL injuries in the mid-portion and on the femoral side may be treated with conservative therapy for spontaneous healing.
• Structural and pathological changes in the enthesis are influenced by the muscle contraction type during exercise.

  Kaichi Ozone, Takanori Kokubun, Kei Takahata, Haruna Takahashi, Moe Yoneno, Yuichiro Oka, Yuki Minegishi, Kohei Arakawa, Takuma Kano, Kenji Murata, Naohiko Kanemura

  Journal of orthopaedic research : official publication of the Orthopaedic Research Society 40 (9) 2076 - 2088 2021/12/04 [Refereed]
   

  Mechanical stress is involved in the onset of sports-related enthesopathy. Although the amount of exercise undertaken is a recognized problem during disease onset, changes in muscle contraction type are also involved in the increase in mechanical stress during exercise. This study aimed to clarify the effects of increased mechanical stress associated with muscle contraction type and amount of exercise on enthesis. Twenty mice underwent treadmill exercise, and the muscle contraction type and overall load during exercise were adjusted by varying the angle and speed conditions. Histological analysis was used to the cross-sectional area of the muscle; area of the enthesis fibrocartilage (FC), and expression of inflammation-, degeneration-, and calcification-related factors in the FC area. In addition, the volume and structure of the bone and FC area were examined using microcomputer imaging. Molecular biological analysis was conducted to compare relative expression levels of inflammation and cytokine-related factors in tendons. The Overuse group, which increased the amount of exercise, showed no significant differences in parameters compared to the sedentary mice (Control group). The mice subjected to slow-speed downhill running (Misuse group) showed pathological changes compared to the Control and Overuse groups, despite the small amount of exercise. Thus, the enthesis FC area may be altered by local mechanical stress that would be increased by eccentric muscle contraction rather than by mechanical stress that increases with the overall amount of exercise. Clinical Significance: The muscle contraction type might be more involved in the onset of sports-related enthesopathy rather than the amount of exercise.
• Impact of Controlling Abnormal Joint Movement on the Effectiveness of Subsequent Exercise Intervention in Mouse Models of Early Knee Osteoarthritis.

  Yuichiro Oka, Kenji Murata, Takuma Kano, Kaichi Ozone, Kohei Arakawa, Takanori Kokubun, Naohiko Kanemura

  Cartilage 13 (2_suppl) 1334S-1344S  2021/12 [Refereed]
   

  OBJECTIVE: Moderate mechanical stress is necessary for preserving the cartilage. The clinician empirically understands that prescribing only exercise will progress osteoarthritis (OA) for knee OA patients with abnormal joint movement. When prescribing exercise for OA, we hypothesized that degeneration of articular cartilage could be further prevented by combining interventions with the viewpoint of normalizing joint movement. DESIGN: Twelve-week-old ICR mice underwent anterior cruciate ligament transection (ACL-T) surgery in their right knee and divided into 4 groups: ACL-T, controlled abnormal joint movement (CAJM), ACL-T with exercise (ACL-T/Ex), CAJM with exercise (CAJM/Ex). Animals in the walking group were subjected to treadmill exercise 6 weeks after surgery, which included walking for 18 m/min, 30 min/d, 3 d/wk for 4 weeks. Joint instability was measured by anterior drawer test, and safranin-O staining and immunohistochemical staining were performed. RESULTS: OARSI (Osteoarthritis Research Society International) score of ACL-T/Ex group showed highest among 4 groups (P < 0.001). And CAJM/Ex group was lower than ACL-T/Ex group. Positive cell ratio of IL-1β and MMP-13 in CAJM/Ex group was lower than ACL-T/Ex group (P < 0.05). CONCLUSIONS: We found that the state of the intra-articular environment can greatly influence the effect of exercise on cartilage degeneration, even if exercise is performed under the same conditions. In the CAJM/Ex group where joint movement was normalized, abnormal mechanical stress such as shear force and compression force accompanying ACL cutting was alleviated. These findings may highlight the need to consider an intervention to correct abnormal joint movement before prescribing physical exercise in the treatment of OA.
• Effect of Suppression of Rotational Joint Instability on Cartilage and Meniscus Degeneration in Mouse Osteoarthritis Model

  Kohei Arakawa, Kei Takahata, Yuichiro Oka, Kaichi Ozone, Kzuma Morosawa, Saaya Enomoto, Kenji Murata, Naohiko Kanemura, Takanori Kokubun

  2021/05/27 

  Joint instability and meniscal dysfunction contribute to the onset and progression of knee osteoarthritis (OA). In the destabilization of the medial meniscus (DMM) model, secondary OA occurs due to the rotational instability and increases compressive stress resulting from the meniscal dysfunction. We created a new controlled abnormal tibial rotation (CATR) model that reduces the rotational instability that occurs in the DMM model. So, we aimed to investigate whether rotational instability affects articular cartilage degeneration using the DMM and CATR models, as confirmed using histology and immunohistochemistry. Twelve-week-old male mice were randomized into 3 groups: DMM group, CATR group, and INTACT group (right knee of the DMM group). After 8 and 12 weeks, we performed the tibial rotational test, safranin-O/fast green staining, and immunohistochemical staining for TNF-α and MMP-13. The rotational instability in the DMM group was significantly higher than that of the other groups. And articular cartilage degeneration was higher in the DMM group than in the other groups. However, meniscal degeneration was observed in both DMM and CATR groups. The TNF-α and MMP-13 positive cell rates in the articular cartilage of the CATR group were lower than those in the DMM group. We found that the articular cartilage degeneration was effectively suppressed by controlling the rotational instability caused by meniscal dysfunction. These findings suggest that suppression of rotational instability in the knee joint is an effective therapeutic measure for preventing OA progression.
• Treadmill Exercise after Controlled Abnormal Joint Movement Inhibits Cartilage Degeneration and Synovitis.

  Yuichiro Oka, Kenij Murata, Kaichi Ozone, Takuma Kano, Yuki Minegishi, Aya Kuro-Nakajima, Kohei Arakawa, Takanori Kokubun, Naohiko Kanemura

  Life (Basel, Switzerland) 11 (4) 2021/04/01 [Refereed]
   

  Cartilage degeneration is the main pathological component of knee osteoarthritis (OA), but no effective treatment for its control exists. Although exercise can inhibit OA, the abnormal joint movement with knee OA must be managed to perform exercise. Our aims were to determine how controlling abnormal joint movement and treadmill exercise can suppress cartilage degeneration, to analyze the tissues surrounding articular cartilage, and to clarify the effect of treatment. Twelve-week-old ICR mice (n = 24) underwent anterior cruciate ligament transection (ACL-T) surgery on their right knees and were divided into three groups as follows: ACL-T, animals in the walking group subjected to ACL-T; controlled abnormal joint movement (CAJM), and CAJM with exercise (CAJM + Ex) (n = 8/group). Walking-group animals were subjected to treadmill exercise 6 weeks after surgery, including walking for 18 m/min, 30 min/day, 3 days/week for 8 weeks. Safranin-O staining, hematoxylin-eosin staining, and immunohistochemical staining were performed. The OARSI (Osteoarthritis research Society international) score was lower in the CAJM group than in the ACL-T group and was even lower in the CAJM + Ex group. The CAJM group had a lower meniscal injury score than the ACL-T group, and the CAJM + Ex group demonstrated a less severe synovitis than the ACL-T and CAJM groups. The observed difference in the perichondrium tissue damage score depending on the intervention method suggests different therapeutic effects, that normalizing joint motion can solve local problems in the knee joint, and that the anti-inflammatory effect of treadmill exercise can suppress cartilage degeneration.
• Effect of Various Types of Muscle Contraction with Different Running Conditions on Mouse Humerus Morphology.

  Kaichi Ozone, Yuichiro Oka, Yuki Minegishi, Takuma Kano, Takanori Kokubun, Kenji Murata, Naohiko Kanemura

  Life (Basel, Switzerland) 11 (4) 2021/03/27 [Refereed]
   

  How various types of muscle contraction during exercises affect bone formation remains unclear. This study aimed to determine how exercises with different muscle contraction types affect bone morphology. In total, 20 mice were used and divided into four groups: Control, Level, Down Slow, and Down. Different types of muscle contraction were induced by changing the running angle of the treadmill. After the intervention, micro-computed tomography (Micro-CT), tartrate-resistant acid phosphatase/alkaline phosphatase (ALP) staining, and immunohistochemical staining were used to analyze the humerus head, tendon-to-bone attachment, and humerus diaphyseal region. Micro-CT found that the volume ratio of the humeral head, the volume of the tendon-to-bone attachment region, and the area of the humeral diaphyseal region increased in the Down group. However, no difference was detected in bone morphology between the Level and Down Slow groups. In addition, histology showed activation of ALP in the subarticular subchondral region in the Down Slow and Down groups and the fibrocartilage region in the tendon-to-bone attachment. Moreover, Osterix increased predominantly in the Down Slow and Down groups.Overall bone morphological changes in the humerus occur only when overuse is added to EC-dominant activity. Furthermore, different type of muscle contractile activities might promote bone formation in a site-specific manner.
• Effects of exercise therapy on joint instability in patients with osteoarthritis of the knee: A systematic review

  Sora Kawabata, Kenji Murata, Kouki Nakao, Moeka Sonoo, Yuri Morishita, Yuichiro Oka, Keisuke Kubota, Aya Kuroo-Nakajima, Shunsuke Kita, Sumika Nakagaki, Kohei Arakawa, Takanori Kokubun, Naohiko Kanemura

  Osteoarthritis and Cartilage Open 2 (4) 100114 - 100114 2665-9131 2020/12 [Refereed]
   

  OBJECTIVE: Abnormal load stress caused by joint instability has been reported to be one of the factors responsible for the development of osteoarthritis (OA). However, few studies have investigated the efficacy of exercise therapy for patients with knee instability-induced OA, and there are no specific treatment guidelines or effects for this form of OA. Therefore, the purpose of this study was to examine the effect of exercise treatments for joint instability in patients with knee OA by a systematic review. DESIGN: Systematic review. RESULTS: Searches in three databases, PubMed, Cochrane, and the Physiotherapy Evidence Database, yielded 14 articles that were scrutinized, and 6 articles that met the inclusion criteria were selected. CONCLUSIONS: Exercise therapy focusing on joint instability, including muscle maintenance and strength training, and specific training targeting knee instability have no additional beneficial effects on knee joint instability. However, because of the benefits of treatment protocols based on patient attributes in exercise treatment focused on joint instability, it is necessary to investigate the effects in more detail in the future.
• Controlling joint instability after anterior cruciate ligament transection inhibits transforming growth factor-beta-mediated osteophyte formation

  K. Murata, T. Kokubun, K. Onitsuka, Y. Oka, T. Kano, Y. Morishita, K. Ozone, N. Kuwabara, J. Nishimoto, T. Isho, K. Takayanagi, N. Kanemura

  Osteoarthritis and Cartilage 27 (8) 1185 - 1196 1063-4584 2019/08 [Refereed]
   

  OBJECTIVE: Abnormal joint instability contributes to cartilage damage and osteophyte formation. We investigated whether controlling joint instability inhibited chronic synovial membrane inflammation and delayed osteophyte formation and examined the role of transforming growth factor-beta (TGF-β) signaling in the associated mechanism. DESIGN: Rats (n = 94) underwent anterior cruciate ligament (ACL) transection. Anterior tibial instability was either controlled (CAM group) or allowed to continue (SHAM group). At 2, 4, and 8 weeks after surgery, radiologic, histopathologic, immunohistochemical, immunofluorescent, and enzyme-linked immunosorbent assay examinations were performed to evaluate osteophyte formation and TGF-β signaling. RESULTS: Joint instability increased cartilage degeneration score and osteophyte formation, and cell hyperplasia and proliferation and synovial thickening were observed in the synovial membrane. Major findings were increased TGF-β expression and Smad2/3 following TGF-β phosphorylation in synovial membarene, articular cartilage, and the posterior tibial growth plate (TGF-β expression using ELISA: 4 weeks; P = 0.009, 95% CI [260.1-1340.0]) (p-Smad2/3 expression density: 4 weeks; P = 0.024, 95% CI [1.67-18.27], 8 weeks; P = 0.034, 95% CI [1.25-25.34]). However, bone morphogenetic protein (BMP)-2 and Smad1/5/8 levels were not difference between the SHAM model and the CAM model. CONCLUSIONS: This study showed that the difference between anterior tibial instability caused a change in the expression level of TGF in the posterior tibia and synovial membrane, and the reaction might be consequently involved in osteophyte formation.
• 損傷部位の違いは前十字靭帯の自己治癒能に影響を及ぼすか

  加納 拓馬, 国分 貴徳, 村田 健児, 岡 優一郎, 小曽根 海知, 森下 佑里, 西元 淳司, 桑原 希望, 高柳 清美, 金村 尚彦

  関東甲信越ブロック理学療法士学会 社団法人 日本理学療法士協会関東甲信越ブロック協議会 37 0142  0916-9946 2018
• メカニカルストレスの増加がEnthesisに与える影響

  小曽根 海知, 国分 貴徳, 林 弘之, 村田 健児, 加納 拓馬, 岡 優一郎, 金村 尚彦

  関東甲信越ブロック理学療法士学会 社団法人 日本理学療法士協会関東甲信越ブロック協議会 37 0140  0916-9946 2018
• Key Determinants of Anterior Cruciate Ligament Spontaneous Healing

  Takanori Kokubun, Naohiko Kanemura, Kenji Murata, Hitomi Shono, Takuma Kanoh, Yuichiro Oka, Kaichi Ozone, Yuri Morishita, Hiroyuki Hayashi, Kiyomi Takayanagi

  Journal of Osteoporosis and Physical Activity 05 (04) 2017 [Refereed]
  

Conference Activities & Talks

• Effect of suppression of joint instability on cartilage and meniscus degeneration

  K Arakawa, K Takahata, Y Oka, K Ozone, S Nakagaki, K Morosawa, K Murata, N Kanemura, T Kokubun

  Orthopaedic Research Society (ORS) 2021  2021/02
• 運動強度を考慮した介入は疼痛管理に寄与するか -実験動物を用いた研究-

  中垣澄香, 岡優一郎, 峯岸雄基, 小曽根海知, 村田健児, 国分貴徳, 金村尚彦

  第29回埼玉県理学療法学会, 埼玉 (オンデマンド)  2021/01
• 変形性膝関節症に対する関節運動の正常化とトレッドミル運動の効果

  岡優一郎, 村田健児, 中垣澄香, 小曽根海知, 峯岸雄基, 黒尾彩, 荒川 航平, 国分貴徳, 金村尚彦

  第29回埼玉県理学療法学会, 埼玉 (オンデマンド)  2021/01
• 遠心性収縮運動の強度及び頻度の違いが腱骨付着部に及ぼす影響

  小曽根海知, 国分貴徳, 高畠啓, 高橋花菜, 米野萌恵, 岡優一郎, 峯岸雄基, 荒川 航平, 村田健児, 金村尚彦

  第29回埼玉県理学療法学会, 埼玉 (オンデマンド)  2021/01
• 半月板機能不全による関節不安定性の制動が軟骨変性因子に与える影響

  荒川航平, 高畠啓, 岡優一郎, 小曽根海知, 中垣澄香, 村田健児, 金村尚彦, 国分貴徳

  第29回埼玉県理学療法学会, 埼玉 (オンデマンド)  2021/01
• 関節不安定性の制動における滑膜の炎症性サイトカインを抑制効果について

  村田健児, 岡優一郎, 加納拓馬, 森下佑里, 黒尾彩, 荒川航平, 中垣澄香, 小曽根海知, 峯岸雄基, 国分貴徳, 金村尚彦

  第29回埼玉県理学療法学会, 埼玉 (オンデマンド)  2021/01
• 半月板機能不全による関節不安定性と圧縮応力の増大が関節軟骨変性に与える影響

  荒川航平, 岡優一郎, 小曽根海知, 中垣澄香, 高畠啓, 村田健児, 金村 尚彦, 国分貴徳

  第25回日本基礎理学療法学術大会, 仙台（オンデマンド）  2020/12
• 遠心性収縮優位な持続的運動は腱付着部炎を誘発する

  小曽根海知, 国分貴徳, 岡優一郎, 峯岸雄基, 村田健児, 金村 尚彦

  第25回日本基礎理学療法学術大会, 仙台（オンデマンド）  2020/12
• ラット膝前十字靭帯損傷モデルにおける自己治癒靭帯の神経再生への影響

  宇都弥紀, 峯岸雄基, 西元淳司, 岡優一郎, 国分貴徳, 村田健児, 金村 尚彦

  第25回日本基礎理学療法学術大会, 仙台（オンデマンド）  2020/12
• 異なる脱神経期間のラット坐骨神経圧挫モデルに対する運動介入 が再神経支配と脊髄神経回路の可塑性に及ぼす影響

  峯岸雄基, 西元淳司, 宇都弥紀, 小曽根海知, 岡優一郎, 村田健児, 国分貴徳, 金村 尚彦

  第25回日本基礎理学療法学術大会, 仙台（オンデマンド）  2020/12
• 関節不安定性の管理はGremlin-1の発現を抑制し 関節軟骨の変性を遅延させる

  岡優一郎, 村田健児, 中垣澄香, 荒川航平, 黒尾彩, 小曽根海知, 峯岸雄基, 国分貴徳, 金村 尚彦

  第25回日本基礎理学療法学術大会, 仙台（オンデマンド）  2020/12
• Impact of controlling abnormal joint movement on the effectiveness of subsequent exercise intervention in mouse model of early knee osteoarthritis

  Y Oka, K Murata, T Kano, K Ozone, K Arakawa, T Kokubun, N Kanemura

  Osteoarthritis Research Society International 2020 World Congress Osteoarthritis Cartilage 28: 471-S472  2020/04
• Effect of joint instability on bone-cartilage degeneration in destabilization of the medial meniscus model

  K Arakawa, T Kokubun, Y Oka, K Ozone, S Nakagaki, K Murata, N Kanemura

  Osteoarthritis Research Society International 2020 World Congress Osteoarthritis Cartilage 28:S214-S215  2020/04
• A quantitative study to examine the effect of controlling abnormal joint instability in a mouse model of anterior cruciate ligament tibial displacement and cartilage degeneration

  T Kokubun, K Arakawa, Y Oka, K Ozone, A Kobayashi, H Takahashi, K Takahata, M Yoneno, K Murata, N Kanemura

  Osteoarthritis Research Society International 2020 World Congress Osteoarthritis Cartilage 28:S212-S213  2020/04
• Controlling joint instability after anterior cruciate ligament transection inhibits the transforming growth factor-beta-mediated osteophyte formation

  K Murata, Y OKa, K Onitsuka, T Kokubun, A Nakajima, K Arakawa, S Nakagaki, N Kenamura

  Osteoarthritis Research Society International 2020 World Congress Osteoarthritis Cartilage 28:S204  2020/04
• 末梢神経損傷後の運動介入が神経再生中の組織内微小環境に及ぼす影響

  桑原希望, 西元淳司, 小曽根海知, 岡優一郎, 加納拓馬, 宇都弥紀, 峯岸雄基, 村田健児, 国分貴徳, 金村尚彦

  第26日本基礎理学療法学術大会, 新潟  2019/11
• 遠心性収縮は筋を肥大させるが骨付着部（Enthesis部）には構造的変化を引き起こす

  伊藤遼佑, 小曽根海知, 岡優一郎, 村田健児, 金村尚彦, 国分貴徳

  第38回関東甲信越ブロック理学療法士学会,群馬  2019/10
• The Effect of Different Injured Sites on Spontaneous Healing Ability in Complete-Rupture ACL

  T Kano, T Kokubun, K Murata, Y Oka, K Ozone, K Takayanagi, N Kanemura

  Orthopaedic Research Society (ORS) 2019 Annual Meeting, Austin, USA  2019/02
• 異常関節運動制動後の運動療法は軟骨の変性を抑制する

  岡優一郎, 国分貴徳, 村田健児, 加納拓馬, 小曽根海知, 荒川航平, 西元淳司, 桑原希望, 金村尚彦

  第27回埼玉県理学療法学会, 埼玉  2019/01
• 自己治癒前十字靭帯の力学的特性に対して治癒期間が与える影響

  加納拓馬, 国分貴徳, 村田健児, 岡優一郎, 小曽根海知, 根本由季菜, 荒川 航平, 森下佑里, 西元淳司, 桑原希望, 髙栁清美, 金村尚彦

  第27回埼玉県理学療法学会, 埼玉  2019/01
• 損傷部位の違いは前十字靭帯の自己治癒能に影響を及ぼすか

  加納拓馬, 国分貴徳, 村田健児, 岡優一郎, 小曽根海知, 森下佑里, 西元淳司, 桑原希望, 高柳清美, 金村尚彦

  第37回関東甲信越ブロック理学療法士学会、栃木  2018/09
• Enthesis構造は機械的ストレスの増加によって変化する

  小曽根海知, 国分貴徳, 林弘之, 村田健児, 加納拓馬, 岡優一郎, 金村尚彦

  第37回関東甲信越ブロック理学療法士学会、栃木  2018/09
• 異常関節運動の制動は変性軟骨に対して保護作用を持つのか？

  岡優一郎, 国分貴徳, 村田健児, 加納拓馬, 小曽根海知, 西元敦司, 宇都弥紀, 峯岸雄基, 金村尚彦

  第37回関東甲信越ブロック理学療法士学会、栃木  2018/09
• 変形性膝関節症動物モデルにおける関節運動の正常化がBMP-2/Smad mRNA発現量に及ぼす影響

  村田健児, 岡優一郎, 加納拓馬, 国分貴徳, 鬼塚勝哉, 森下佑里, 小曽根海知, 桑原希望, 西元淳司, 藤原秀平, 中島彩, 高柳清美, 金村尚彦

  第37回関東甲信越ブロック理学療法士学会、栃木  2018/09
• Gene expressions dynamics in nerve regeneration after anterior crucite ligament injury in a rat model

  N Kanemura, T Kokubun, Y Morishita, K Murata, Y Shimahara, A Nakajima, Y Oka, K Takayanagi

  12th World Congress of the International Society of Physical and Rehabilitation Medicine (ISPRM 2018), Paris, France.  2018/07
• Integrin and Fibronectin guide bridging movement of remnants during anterior cruciate ligament spontaneous healing in rat model

  Takanori Kokubun, H. Shono, Y. Morishita, N. Kanemura, K. Murata, T. Kano, K. Ozone, Y. Oka, H. Hayashi, K. Takayanagi

  12th World Congress of the International Society of Physical and Rehabilitation Medicine (ISPRM 2018), Paris, France.  2018/07
• Improvement in joint instability reduces inflammatory pain of early degenerative knee osteoarthritis

  A Nakajima, K Murata, Y Morishita, T, Kokubun, Y Oka, N Kanemura

  12th World Congress of the International Society of Physical and Rehabilitation Medicine (ISPRM 2018), Paris, France.  2018/07
• Gene Expression Analysis Identifies Key Genes For Spontaneous Healing Anterior Cruciate Ligament After Complete Injury In Rats

  T Kokubun, H Shono, Y Morishita, N Kanemura, K Murata, T Kano, K Ozone, Y Oka, H Hayashi, K Takayanagi

  Orthopaedic Research Society Annual meeting 2018  2018/03
• Validation Verification Of Controlled Abnormal Joint Movement Model In Mice

  Y Oka, T Kokubun, K Murata, T. Kano, K Ozone, N Kanemura

  Orthopaedic Research Society Annual meeting 2018  2018/03
• Activation of neuroplasticity pathways in the rat spinal cord through treadmill exercise

  Y Oka, Y Shirose, N Kuwabara, K Nakamoto, T Kokubun, K Murata, N Kanemura

  Science for Neuroscience 47th annual meeting,USA  2017/11
• 異なる週齢ラットに対する同強度の運動介入がPI3K/Akt 経路の活性化に与える影響

  岡優一郎, 白勢陽子, 桑原希望, 木曽波音, 中本幸太, 国分貴徳, 村田健児, 金村尚彦

  第36回関東甲信越ブロック理学療法士学会．長野  2017/09

MISC

• メカニカルストレスと理学療法—特集 運動器理学療法をどう捉えるか : 統合的戦略で自らの思考の枠を乗り越える

  金村 尚彦, 久保田 圭祐, 加納 拓馬, 森下 佑里, 岡 優一郎, 小曽根 海知, 峯岸 雄基, 村田 健児  理学療法ジャーナル  57-  (9)  1057  -1063  2023/09
• 保存治癒ACLの組織強度に運動負荷が与える影響

  加納 拓馬, 国分 貴徳, 村田 健児, 岡 優一郎, 小曽根 海知, 森下 佑里, 金村 尚彦, 高柳 清美  理学療法-臨床・研究・教育  28-  (1)  93  -95  2021/03
• スポーツ障害の発症にはOveruseよりもMisuseが影響を及ぼす

  小曽根 海知, 国分 貴徳, 岡 優一郎, 金村 尚彦  理学療法-臨床・研究・教育  28-  (1)  107  -108  2021/03
• 末梢神経損傷後の運動介入が神経再生中の組織内微小環境に及ぼす影響

  桑原 希望, 西元 淳司, 小曽根 海知, 岡 優一郎, 加納 拓馬, 宇都 弥紀, 峯岸 雄基, 村田 健児, 国分 貴徳, 金村 尚彦  理学療法学  47-  (Suppl.1)  171  -171  2021/03
• 前十字靱帯損傷後の関節制動が筋萎縮関連タンパク質に及ぼす影響

  村田 健児, 岡 優一郎, 加納 拓馬, 藤原 秀平, 金村 尚彦  理学療法-臨床・研究・教育  27-  (1)  31  -35  2020/03  

  【はじめに】前十字靱帯を損傷させた後に脛骨前方不安定性を制動した場合、大腿直筋の筋萎縮関連因子の変化についてタンパク質・mRNA解析によって調査した。【方法】10週齢Wistar系雄性ラット(n=24)の前十字靱帯を断裂させることで惹起した脛骨の前方不安定性を制動した群、脛骨の前方不安定性が残存したSham群に分類した。術後4、8週(各群・週齢n=6)で大腿直筋を採取し、リアルタイムPCR法とウェスタンブロッド法でAtrogin-1ならびにMuRF-1について解析した。【結果】mRNAについてAtrogin-1とMuRF-1は統計学的有意差を認めなかった。タンパク質解析ではAtrogin-1(p=0.001)ならびにMuRF-1(p<0.001)において8週で有意に発現した。【結論】靱帯損傷後の早期の関節制動は大腿直筋の筋萎縮関連因子Atrogin-1ならびにMuRF-1を抑制した。(著者抄録)
• Enthesopathy発症要因の解明に向けた動物実験モデルの確立

  小曽根 海知, 国分 貴徳, 林 弘之, 加納 拓馬, 岡 優一郎, 金村 尚彦  理学療法学  46-  (Suppl.1)  2  -6  2019/08
• 異常関節運動の制動は変性軟骨に対して保護作用を持つのか？

  岡 優一郎, 国分 貴徳, 村田 健児, 加納 拓馬, 小曽根 海知, 西元 敦司, 宇都 弥紀, 峯岸 雄基, 金村 尚彦  関東甲信越ブロック理学療法士学会  37-  143  -143  2018

Research Grants & Projects

• マクロファージの賦活が創傷治癒メカニズムを介して軟骨代謝へ与える影響の探索

  日本学術振興会：科学研究費助成事業 若手研究

  Date (from‐to) : 2023/04 -2026/03 

  Author : 岡 優一郎
• 変形性関節症に対する運動療法から迫るマクロファージを介した軟骨保護作用の解明

  日本学術振興会：科学研究費助成事業 研究活動スタート支援

  Date (from‐to) : 2022/08 -2024/03 

  Author : 岡 優一郎
• 関節運動の正常化は軟骨の変性を予防するのか？―早期OAマウスモデルを用いた研究―

  日本理学療法士協会：理学療法にかかわる研究助成

  Date (from‐to) : 2019/07 -2020/03
• 軟骨変性に関わる組織の探索

  埼玉県理学療法士会：

  Date (from‐to) : 2019/05 -2020/03