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Development of HIF-1a-induced exercise therapy focusing on the intra-articular hypoxic environment

Research Project

Project/Area Number 17H02136
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Rehabilitation science/Welfare engineering
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Arai Yuji  京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449)

Co-Investigator(Kenkyū-buntansha) 久保 俊一  京都府立医科大学, 医学(系)研究科(研究院), 特任教授 (20178031)
中川 周士  京都府立医科大学, 医学(系)研究科(研究院), 助教 (30643382)
井上 裕章  京都府立医科大学, 医学(系)研究科(研究院), 助教 (60457968)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2019: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2018: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2017: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Keywords軟骨 / 低酸素環境 / メカニカルストレス / 伸展刺激 / HIF-1α / 運動療法 / 低酸素 / 軟骨代謝 / 整形外科 / リハビリテーション / ストレス
Outline of Final Research Achievements

Intermittent mechanical stress was applied using an automated stretching culture apparatus under normoxia (21%) and hypoxia (5%). The gene expression differed according to the oxygen environment, extension intensity, and stimulation time, and the mechanism of chondrocyte response for mechanical stress under hypoxic conditions was different from that under normoxia. In the hypoxic environment, HIF-1α was significantly increased, anabolic factor was increased, and catabolic factor was decreased when mechanical stress was applied. In a hypoxic environment, HIF-1α may regulate cartilage substrate metabolism.

Academic Significance and Societal Importance of the Research Achievements

本研究で得られた知見により,運動療法のメカニズムが究明できれば,OA の発症,進行を予防できる新たな運動療法の道が拓ける.さらに本研究の先には,現行の薬物療法と組み合わせることで相乗的に anabolic な効果を得られる革新的な運動療法が開発できる可能性もある.本研究の成果により健康寿命の延長をもたらし,年々増加する医療費の抑制に繋がることが期待される.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (13 results)

All 2020 2019 2018 2017

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (10 results) (of which Int'l Joint Research: 5 results)

  • [Journal Article] Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models2019

    • Author(s)
      Fujii Yuta、Inoue Hiroaki、Arai Yuji、Shimomura Seiji、Nakagawa Shuji、Kishida Tsunao、Tsuchida Shinji、Kamada Yoichiro、Kaihara Kenta、Shirai Toshiharu、Terauchi Ryu、Toyama Shogo、Ikoma Kazuya、Mazda Osam、Mikami Yasuo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 20 Issue: 20 Pages: 5100-5100

    • DOI

      10.3390/ijms20205100

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The tetraspanin CD81 mediates the growth and metastases of human osteosarcoma2019

    • Author(s)
      Mizoshiri Naoki、Shirai Toshiharu、Terauchi Ryu、Tsuchida Shinji、Mori Yuki、Hayashi Daichi、Kishida Tsunao、Arai Yuji、Mazda Osam、Nakanishi Tohru、Kubo Toshikazu
    • Journal Title

      Cellular Oncology

      Volume: 42 Issue: 6 Pages: 861-871

    • DOI

      10.1007/s13402-019-00472-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Treadmill Running Ameliorates Destruction of Articular Cartilage and Subchondral Bone, Not Only Synovitis, in a Rheumatoid Arthritis Rat Model.2018

    • Author(s)
      Shimomura S, Inoue H, Arai Y, Nakagawa S, Fujii Y, Kishida T, Ichimaru S, Tsuchida S, Shirai T, Ikoma K, Mazda O, Kubo T.
    • Journal Title

      Int J Mol Sci

      Volume: 19 Issue: 6 Pages: 1653-1653

    • DOI

      10.3390/ijms19061653

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Analysis Of Reaction To Tensile Stress In Chondrocytes In Hypoxic Environment2020

    • Author(s)
      Kamada Yoichiro、Inoue Hiroaki、Arai Yuji、Shimomura Seiji、Nakagawa Shuji、Tsuchida Shinji、Fujii Yuta、Kaihara Kenta、Mazda Osam、Mikami Yasuo
    • Organizer
      66th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Effect Of Hif-1α Stabilization By Deferoxamine On Chondrocyte And Articular Cartilage2020

    • Author(s)
      Kaihara Kenta、Nakagawa Shuji、Arai Yuji、Fujii Yuta、Inoue Hiroaki、Tsuchida Shinji、Kamada Yoichiro、Mazda Osam、Mikami Yasuo
    • Organizer
      66th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 低酸素環境下における伸展刺激に対する軟骨細胞のストレス応答解析2019

    • Author(s)
      鎌田陽一郎、井上裕章、新井祐志、下村征史、中川周士、土田真嗣、松田 修、久保俊一
    • Organizer
      日本整形外科学会基礎学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Hypoxic Condition Promotes Differentiation From Human iPSC to Cartilage2019

    • Author(s)
      Shimomura S, Inoue H, Arai Y, Nakagawa S, Tsuchida S, Ichimaru S, Fujii Y, Mazda O, Kubo T
    • Organizer
      65th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2018 Annual Research Report
  • [Presentation] HIF-1α in articular cartilage is up-regulated by treadmill running in vivo2018

    • Author(s)
      Fujii Y, Inoue H, Arai Y, Nakagawa S, Tsuchida S, Shimomura S, Mazda O, Kubo T
    • Organizer
      21st World Congress of the Osteoarthritis Research Society International (OARSI)
    • Related Report
      2018 Annual Research Report
  • [Presentation] Histological evaluation of treadmill running on knee joint of rat arthritis model2018

    • Author(s)
      Fujii Y, Inoue H, Arai Y, Nakagawa S, Tsuchida S, Shimomura S, Mazda O, Kubo T
    • Organizer
      26th Annual Meeting of European Orthopaedic Reserch Society
    • Related Report
      2018 Annual Research Report
  • [Presentation] トレッドミル走行がラット関節炎モデルの膝関節に与える組織学的評価2018

    • Author(s)
      藤井雄太,井上裕章,新井祐志,中川周士,土田真嗣,下村征史,松田 修,久保俊一
    • Organizer
      第33回日本整形外科基礎学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Effects of hypoxic conditions in differentiation of human iPSC to cartilage2018

    • Author(s)
      Seiji Shimomura, Hiroaki Inoue, Yuji Arai, Shuji Nakagawa, Shinji Tsuchida,Shohei Ichimaru, Yuta Fujii, Osamu Mazda, Toshikazu Kubo
    • Organizer
      64th Annual Meeting of Orthopaedic Research Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The effect of treadmill running on knee articular cartilage in rats2017

    • Author(s)
      Seiji Shimomura, Hiroaki Inoue, Yuji Arai, Shuji Nakagawa, Shinji Tsuchida, Shohei Ichimaru, Osam Mazda, Toshikazu Kubo
    • Organizer
      20th World Congress of the Osteoarthritis Research Society International (OARSI)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Regulation of inflammatory cytokine expression and osteoclastgenesis by gap junctional protein in vitro and in vivo.2017

    • Author(s)
      Seiji Shimomura, Shinji Tsuchida, Yuji Arai, Shuji Nakagawa, Hiroaki Inoue, Shohei Ichimaru, Yuta Fujii, Osam Mazda, Toshikazu Kubo
    • Organizer
      The 5th annual meeting of the international cytokine and interferon society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research

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Published: 2017-04-28   Modified: 2021-02-19  

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