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Challenging to explore a prevention strategy for Knee osteoarthritis using an experimental animal model and patient analysis

Research Project

Project/Area Number 21K19724
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 59:Sports sciences, physical education, health sciences, and related fields
Research InstitutionSaitama Prefectural University

Principal Investigator

Kokubun Takanori  埼玉県立大学, 保健医療福祉学部, 准教授 (10616395)

Co-Investigator(Kenkyū-buntansha) 中村 高仁  埼玉県立大学, 保健医療福祉学部, 助教 (70847962)
Project Period (FY) 2021-07-09 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords変形性膝関節症 / 実験動物モデル / メカニカルストレス / MRI / 骨病変 / 軟骨変性 / 膝関節屈曲モーメント / 膝関節内反モーメント / 動作解析 / 軟骨下骨 / 発症予防 / 剪断力 / 圧迫力 / メカノバイオロジー / バイオメカニクス
Outline of Research at the Start

本研究では,推定患者数が2,500万人超とも言われ,今や国民病と言っても過言ではない変形性膝関節症の発症メカニズムを,運動と生体反応の視点から解明に挑む.変形性膝関節症の近年の研究は,再生医療の発展を背景とした軟骨再生治療が本邦では世界をリードしているが,日本人特有の生活習慣から欧米とは異なる発症メカニズムが想定される我が国では,治療以前に発症を予防することが最も重要であると考えている.そこで本研究では,実験動物を対象とした基礎的な疾患メカニズム解明と,実際の患者さんを対象とした医学データおよび運動学動作解析などのバイオメカニクス的手法を駆使し,発症予防戦略の糸口を掴むことを目指す.

Outline of Final Research Achievements

In this study, we analyzed the relationship between the type of mechanical stress and the onset location of knee degeneration to reveal the onset mechanism of knee osteoarthritis(OA). Our results suggested that the shear stress or compression stress induced degeneration in the specific location of rodent knees. Next, we analyzed the MRI imaging and gait biomechanics of early knee OA patients and age-matched adults. These results showed changing the gait kinematic components, like knee flexion moment and knee abduction moment related to the location of degeneration.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は,膝関節に生じるメカニカルストレスの違いが,異なる病態発生開始部位から変形性膝関節症の発生に至る可能性を示唆している.現時点では因果関係までを完全に明らかにできているわけではないが,メカニカルストレスの種類と病態発生部位に一定の関係性を認めた点は,今後変形性膝関節症の発症予防法確立へ向けた方略の確立に貢献しうる,また,早期の変形性膝関節症患者および,変形性膝関節症とは診断されていない高齢者においてMRI画像により検出された病変部位と歩行動作の特徴量に関連が認められたことは,今後歩行動作の異常から早期に変形性膝関節症のリスクを診断し,予防を目指した介入を行うための基盤となる.

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (51 results)

All 2024 2023 2022 2021 Other

All Int'l Joint Research (2 results) Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 4 results) Presentation (40 results) (of which Int'l Joint Research: 17 results) Remarks (4 results)

  • [Int'l Joint Research] university of California, Davis(米国)

    • Related Report
      2023 Annual Research Report
  • [Int'l Joint Research] University of California Davis(米国)

    • Related Report
      2022 Research-status Report
  • [Journal Article] Concurrent Joint Contact in Anterior Cruciate Ligament Injury induces cartilage micro-injury and subchondral bone sclerosis, resulting in knee osteoarthritis2024

    • Author(s)
      Takahata Kei、Lin Yu-Yang、Osipov Benjamin、Arakawa Kohei、Enomoto Saaya、Christiansen Blaine A.、Kokubun Takanori
    • Journal Title

      bioRxiv

      Volume: 0 Pages: 0-0

    • DOI

      10.1101/2024.05.08.593114

    • Related Report
      2023 Annual Research Report
    • Open Access / Int'l Joint Research
  • [Journal Article] Joint instability causes catabolic enzyme production in chondrocytes prior to synovial cells in novel non-invasive ACL ruptured mouse model2023

    • Author(s)
      Takahata K.、Arakawa K.、Enomoto S.、Usami Y.、Nogi K.、Saitou R.、Ozone K.、Takahashi H.、Yoneno M.、Kokubun T.
    • Journal Title

      Osteoarthritis and Cartilage

      Volume: 31 Issue: 5 Pages: 576-587

    • DOI

      10.1016/j.joca.2022.12.004

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The difference in joint instability affects the onset of cartilage degeneration or subchondral bone changes2022

    • Author(s)
      Arakawa K,Takahata K, Enomoto S, Oka Y, Ozone K, Nakagaki S, Murata K, Kanemura N, Kokubun T
    • Journal Title

      Osteoarthritis and Cartilage

      Volume: 30 Issue: 3 Pages: 451-460

    • DOI

      10.1016/j.joca.2021.12.002

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Effect of Suppression of Rotational Joint Instability on Cartilage and Meniscus Degeneration in Mouse Osteoarthritis Model2022

    • Author(s)
      Arakawa K,Takahata K, Enomoto S, Oka Y, Ozone K, Morosawa K, Murata K, Kanemura N, Kokubun T
    • Journal Title

      Cartilage

      Volume: 13 Issue: 1 Pages: 1-11

    • DOI

      10.1177/19476035211069239

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 関節制動による関節不安定性の違いが関節軟骨・半月板に与える影響2021

    • Author(s)
      諸沢 和真, 荒川 航平, 国分 貴徳
    • Journal Title

      Rigakuryoho-Rinsho, Kenkyu, Kyoiku

      Volume: 28 Issue: 1 Pages: 62-68

    • DOI

      10.11350/ptcse.28.62

    • NAID

      130008023380

    • ISSN
      1880-893X, 1880-8948
    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Presentation] Comparison of Compression and Non-Compression Anterior Cruciate Ligament Rupture Models in Mice2024

    • Author(s)
      Kei Takahata, Yu-Yang Lin, Benjamin, Kohei Arakawa, Saaya Enomoto, Blaine A. Christiansen, Takanori Kokubun
    • Organizer
      2024 OARSI World Congress on Osteoarthritis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Compressive ACL rupture model induced early knee Osteoarthritis2024

    • Author(s)
      高畠啓,Yu-Yang Lin,Benjamin Osipov,荒川航平,榎本沙彩,Blaine Christiansen,国分貴徳
    • Organizer
      第36回日本軟骨代謝学会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Development of the Novel Prolonged Progressive Osteoarthritis Model to Elucidate the Onset Mechanism of Primary Knee Osteoarthritis2024

    • Author(s)
      Enomoto S, Arakawa K,Takahata K, Saitou R, Miyamoto H, Yuna Usami, Kokubun T
    • Organizer
      ORS 2024 Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 培養基材の硬度は軟骨細胞のメカノレスポンスに影響を与える2023

    • Author(s)
      荒川航平,大山智子,高畠啓,国分貴徳
    • Organizer
      第29回日本基礎理学療法士学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] メカニカルストレスの減少は股関節の発達・形成における軟骨内骨化プロセスを遅延させる2023

    • Author(s)
      荒川航平,国分貴徳
    • Organizer
      第29回日本基礎理学療法士学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 一次性変形性膝関節症の発症メカニズム探索に向けた緩徐進行モデルマウスの開発2023

    • Author(s)
      榎本沙彩, 荒川航平,高畠啓, 斉藤陸,宮本ひまり,野木康陽,宇佐美優奈,国分貴徳
    • Organizer
      第29回日本基礎理学療法士学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 関節不安定性を伴う膝関節において急性期滑膜炎は長期的な軟骨変性に寄与しない2023

    • Author(s)
      高畠啓,荒川航平,榎本沙彩,米野萌恵,宇佐美優奈,髙橋花奈,国分貴徳
    • Organizer
      第29回日本基礎理学療法士学会学術大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Structural Analysis on Postnatal Cartilage Development of the Patellar Femoral Joint in Mice2023

    • Author(s)
      Hirata S, Takahata K, Yoneno M, Usami Y, Kokubun T.
    • Organizer
      OARSI 2023 World Congress on Osteoarthritis
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Synovial invasion in the ACL-T model might cause unexpected cartilage degeneration in the early stage2023

    • Author(s)
      Takahata K, Arakawa K, Takahashi H, Yoneno M, Kokubun T.
    • Organizer
      OARSI 2023 World Congress on Osteoarthritis
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 基質硬度の違いが培養軟骨細胞の表現型に与える影響2023

    • Author(s)
      荒川航平,大山智子,高畠啓,国分貴徳
    • Organizer
      第35回日本軟骨代謝学会
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Presentation] Posterior Cruciate Ligament Injury Induces Cartilage Degeneration Depending On The Rotational Instability2023

    • Author(s)
      Enomoto S, Arakawa K,Takahata K, Usami Y,Aizawa Y, Saitou R, Kokubun T
    • Organizer
      ORS 2023 Annual Meeting
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Longitudinal Changes of Synovial Fluid in OA Progression Induced by Mechanical Stress2023

    • Author(s)
      Takahata K, Arakawa K, Takahashi H, Yoneno M, Usami Y, Enomoto S, Kokubun T.
    • Organizer
      ORS 2023 Annual Meeting
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of Knee Joint Rotational Instability Associated with Anterior Cruciate Ligament and Medial Collateral Ligament Injury in Rodent Model2023

    • Author(s)
      Miyamoto H, Enomoto S, Saito R, Usami Y, Arakawa K, Kokubun T
    • Organizer
      ORS 2023 Annual Meeting
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] 前十字靭帯・内側側副靭帯がもたらす膝関節回旋運動制動機構の解明~実験動物による前臨床モデル研究~2023

    • Author(s)
      宮本ひまり,榎本沙彩, 斉藤陸,宇佐美優奈,荒川航平,国分貴徳
    • Organizer
      第31回埼玉県理学療法学会
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Presentation] 大腿脛骨関節における関節軟骨を部分欠損させた新たなマウスモデル開発の試み2023

    • Author(s)
      高畠啓,荒川航平,髙橋花奈,米野萌恵,宇佐美優奈,榎本沙彩,国分貴徳
    • Organizer
      第31回埼玉県理学療法学会
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Presentation] 変形性膝関節症マウスモデルにおける週齢の違いが進行速度の差に及ぼす影響の観察2023

    • Author(s)
      榎本沙彩, 荒川航平,高畠啓, 宇佐美優奈, 斉藤陸,野木康陽,国分貴徳
    • Organizer
      第31回埼玉県理学療法学会
    • Related Report
      2023 Annual Research Report 2022 Research-status Report
  • [Presentation] 後十字靭帯損傷が関節軟骨及び軟骨下骨に及ぼす影響の解明2023

    • Author(s)
      榎本沙彩、荒川航平,高畠啓,宇佐美優奈、国分貴徳
    • Organizer
      第35回日本軟骨代謝学会
    • Related Report
      2022 Research-status Report
  • [Presentation] メカニカルストレスの減少が発育期の股関節形成に与える影響2023

    • Author(s)
      荒川航平,大内勇人,高畠啓,国分貴徳
    • Organizer
      第31回埼玉県理学療法学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Analyzing mRNA expression of serum extracellular vesicles in knee osteoarthritis mouse model.2022

    • Author(s)
      Takahata K, Izuo N, Arakawa K, Kokubun T.
    • Organizer
      第9回日本細胞外小胞学会学術集会
    • Related Report
      2022 Research-status Report
  • [Presentation] 異なるモデルにおける部位ごとの脛骨軟骨下骨の骨構造変化の違い2022

    • Author(s)
      荒川航平,高畠啓,榎本沙彩,国分貴徳
    • Organizer
      第27回日本基礎理学療法士学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] メカニカルストレスによる異なる軟骨変性発生プロセス:侵襲モデルと非侵襲モデルを用いた比較検討2022

    • Author(s)
      高畠啓,荒川航平,髙橋花奈,米野萌恵,宇佐美優奈,榎本沙彩,国分貴徳
    • Organizer
      第27回日本基礎理学療法士学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] 後十字靭帯損傷によるメカニカルストレスの変化が膝蓋大腿関節の軟骨及び軟骨下骨に与える影響の長期的観察2022

    • Author(s)
      榎本沙彩, 荒川航平,高畠啓, 宇佐美優奈, 斉藤陸,野木康陽,国分貴徳
    • Organizer
      第27回日本基礎理学療法士学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] メカニカルストレスによる関節軟骨変性の発症に滑膜炎は寄与しない2022

    • Author(s)
      高畠啓,荒川航平,髙橋花奈,米野萌恵,宇佐美優奈,榎本紗彩,国分貴徳
    • Organizer
      第10回日本運動器理学療法学会学術大会
    • Related Report
      2022 Research-status Report
  • [Presentation] SUGGESTION OF NEW PTOA MICE MODEL INDUCED BY MECHANICAL STRESS WITHOUT SURGERY2022

    • Author(s)
      Takahata. K, Arakawa. K, Usami. Y, Takahashi. H, Yoneno. M, Aizawa. Y, Enomoto. S, Saito. R, Murata. K, Kanemura. N, kokubun. T.
    • Organizer
      OARSI world congress on osteoarthritis '22
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] MMP3 IN SYNOVIAL FLUID TENDS TO UPREGULATE PRIOR TO CARTILAGE DEGENERATION WITH MICE OA MODEL.2022

    • Author(s)
      Takahata. K, Arakawa. K, Usami. Y, Takahashi. H, Yoneno. M, Aizawa. Y, Enomoto. S, Saito. R, Murata. K, Kanemura. N, kokubun. T.
    • Organizer
      OARSI world congress on osteoarthritis '22
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] RELATIONSHIP BETWEEN MICE REPRODUCING POSTERIOR CRUCIATE LIGAMENT INJURY AND THE DEVELOPMENT OF KNEE OSTEOARTHRITIS2022

    • Author(s)
      Enomoto S, Arakawa K,Takahata K, Usami Y,Aizawa Y, Saitou R, Kokubun T
    • Organizer
      OARSI world congress on osteoarthritis '22
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] The abnormal patella downward condyle by posterior cruciate ligament dysfunction leads to patellofemoral osteoarthritis in the mice model2022

    • Author(s)
      Enomoto S, Takahata K, Usami Y, Kokubun T
    • Organizer
      OARSI world congress on osteoarthritis '22
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] EFFECT OF SUPPRESSION JOINT INSTABILITY ON SUBCHONDRAL BONE REMODELING2022

    • Author(s)
      Arakawa K, Takahata K, Enomoto S, Murata K, Kanemura N, Kokubun T
    • Organizer
      OARSI world congress on osteoarthritis '22
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of suppression of joint instability in different models on cartilage degeneration and subchondral bone changes2022

    • Author(s)
      Arakawa K,Takahata K, Enomoto S, Nakagaki S, Murata K, Kanemura N, Kokubun T
    • Organizer
      ORS 2022 Annual Meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a mouse model to elucidate the pathogenesis of osteoarthritis of the knee after aposterior cruciate ligament injury2022

    • Author(s)
      Enomoto S, Arakawa K,Takahata K, Usami Y, Aizawa Y, Saito R, Kokubun T
    • Organizer
      ORS 2022 Annual Meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Effect of Abnormal Mechanical Stress on Articular Cartilage Degeneration -with a non-invasive mice model-2022

    • Author(s)
      Takahata K, Arakawa K,Usami Y, Takahashi H, Yoneno M, Aizawa Y, Enomoto S,Saito R, Murata K, Kanemura N, Kokubun T
    • Organizer
      ORS 2022 Annual Meeting
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 異常な関節運動がもたらす関節軟骨変性の機序解明-非侵襲性モデルを用いた新たな検討-2022

    • Author(s)
      高畠啓,荒川航平,宇佐美優奈,髙橋花奈,米野萌恵,村田健児,金村尚彦,国分貴徳
    • Organizer
      第30回埼玉県理学療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 後十字靭帯損傷後の膝蓋大腿関節症発症メカニズム解明に向けたマウスモデルの開発2022

    • Author(s)
      榎本沙彩,荒川航平,高畠啓, 宇佐美優奈,相澤幸夏, 斉藤陸, 国分貴徳
    • Organizer
      第30回埼玉県理学療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 変形性膝関節症発症メカニズム解明に向けた新規マウスモデルの開発2021

    • Author(s)
      榎本沙彩,荒川航平,高畠啓, 宇佐美優奈,相澤幸夏, 斉藤陸, 国分貴徳
    • Organizer
      第26回 日本基礎理学療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 小動物モデルにおける関節液解析手法の新規提案 -ハイドロゲルを用いた検討-2021

    • Author(s)
      高畠啓, 酒井崇匡, 荒川航平, 相澤幸夏, 小島拓真, 村田健児, 金村尚彦, 国分貴徳
    • Organizer
      第26回 日本基礎理学療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] メカニカルストレスの違いが変形性膝関節症発症メカニズムに与える影響2021

    • Author(s)
      荒川航平,高畠啓,岡優一郎,小曽根海知,榎本沙彩,村田健児,金村尚彦,国分貴徳
    • Organizer
      第26回 日本基礎理学療法学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 関節内損傷を伴わない非侵襲的な前十字靭帯損傷モデルの開発2021

    • Author(s)
      高畠啓,荒川航平,小曽根海知,村田健児,金村尚彦,国分貴徳
    • Organizer
      第40回 関東甲信越ブロック 理学療法士学会
    • Related Report
      2021 Research-status Report
  • [Presentation] 関節内損傷を伴わない非侵襲的な前十字靭帯損傷モデルの開発2021

    • Author(s)
      荒川航平,高畠啓,榎本沙彩,村田健児,金村尚彦,国分貴徳
    • Organizer
      第40回 関東甲信越ブロック 理学療法士学会
    • Related Report
      2021 Research-status Report
  • [Presentation] Differences in the progression of articular cartilage and subchondral bone degeneration between mouse models2021

    • Author(s)
      Arakawa K,Takahata K, Oka Y, Ozone K, Enomoto S, Murata K, Kanemura N, Kokubun T
    • Organizer
      OARSI connect virtual world congress on osteoarthritis '21
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] Development of a new method for analysis of the mRNA content of knee synovial fluid2021

    • Author(s)
      Takahata K, Arakawa K, Ozone K, Usami Y, Takahashi H, Yoneno M, , Murata K, Kanemura N, Kokubun T
    • Organizer
      OARSI connect virtual world congress on osteoarthritis '21
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Remarks] 変形性膝関節症の発症・進行予防を目的としたリハビリテーション研究の成果発表

    • URL

      https://www.spu.ac.jp/news/?itemid=1734&dispmid=508

    • Related Report
      2023 Annual Research Report
  • [Remarks] 研究成果のアウトリーチ(所属機関のホームページにて)

    • URL

      https://www.spu.ac.jp/news/?itemid=1734&dispmid=508

    • Related Report
      2022 Research-status Report
  • [Remarks] 変形性膝関節症において、メカニカルストレスの違いは軟骨変性と軟骨下骨変化に異なる影響を及ぼす

    • URL

      https://www.spu.ac.jp/tabid600.html?itemid=1388&dispmid=1828

    • Related Report
      2021 Research-status Report
  • [Remarks] 膝関節の回旋不安定性の抑制が変形性膝関節症モデルマウスの関節軟骨・半月板変性に及ぼす影響

    • URL

      https://www.spu.ac.jp/tabid600.html?itemid=1435&dispmid=1828

    • Related Report
      2021 Research-status Report

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Published: 2021-07-13   Modified: 2025-01-30  

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