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Connexin 43 as a therapeutic target in rheumatoid arthritis

Research Project

Project/Area Number 16K15669
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionKyoto Prefectural University of Medicine

Principal Investigator

Tsuchida Shinji  京都府立医科大学, 医学(系)研究科(研究院), 助教 (10719834)

Research Collaborator ARAI Yuji  
NAKAGAWA Shuji  
INOUE Hiroaki  
TERAUCHI Ryu  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Keywordsconnexin 43 / synovitis / rheumatoid arthritis / 滑膜炎 / connexin43 / 免疫学 / 細胞・組織
Outline of Final Research Achievements

We analyzed the influence of treadmill running on RA joints using CIA rat model. DA rats were randomly divided into four groups: The control group, treadmill group , CIA group, and CIA + treadmill group. Destruction of the ankle joint was evaluated by histological analyses. Morphological changes of subchondral bone were analyzed by μ-CT. CIA treatment-induced synovial membrane invasion, articular cartilage destruction, and bone erosion. Treadmill running improved these changes. The synovial membrane in CIA rats produced a large amount of TNF-α and Connexin 43; production was significantly suppressed by treadmill running. On μ-CT of the talus, BV/TV was significantly decreased in the CIA group. MSV, an index of bone loss, was significantly increased. These changes were significantly improved by treadmill running. These findings indicate that treadmill running in CIA rats inhibited synovial hyperplasia and joint destruction.

Academic Significance and Societal Importance of the Research Achievements

運動療法は安全で簡便に行えることから広く普及しており,RAに対しても運動療法は推奨されているが,適切な強度や運動時間は定まっていない.RA活動期に対する運動は関節破壊を増悪させる危険性もある.そのため,RAに対する効果的な運動療法の開発には,運動が炎症活動期の関節に及ぼす分子生物学的なメカニズムや関節破壊に与える影響を解明することが不可欠である.本研究結果から,RAに対する運動療法を軸としたこれまでにない疾患アプローチを有する細胞間コミュニケーションを制御療法の開発にむけた基礎データを構築できたと考える.

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 2016 Other

All Journal Article (2 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (6 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [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
  • [Journal Article] Expression of connexin 43 in synovial tissue of patients with rheumatoid arthritis.2016

    • Author(s)
      Matsuki T, Arai Y, Tsuchida S, Terauchi R, Oda R, Fujiwara H, Mazda O, Kubo T.
    • Journal Title

      Arch Rheumatol

      Volume: 31 Issue: 1 Pages: 1-4

    • DOI

      10.5606/archrheumatol.2016.5597

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] 関節リウマチ動物モデルにおけるトレッドミル走行の効果2018

    • Author(s)
      土田真嗣,小田 良,新井祐志,遠山将吾,下村征史,徳永大作,久保俊一
    • Organizer
      第21回比叡RAフォーラム
    • 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] 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
    • Int'l Joint Research
  • [Presentation] The effects of treadmill exercise at a single time on knee articular cartilage in vivo2018

    • Author(s)
      Shimomura S, Inoue H, Arai Y, Nakagawa S, Tsuchida S, Ichimaru S, Fujii Y, Mazda O, Kubo T
    • Organizer
      26th Annual Meeting of European Orthopaedic Reserch Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of the expression of connexin 43 in synovial tissue of patients with arthritis2017

    • Author(s)
      Seiji Shimomura, Shinji Tsuchida, Yuji Arai, Shuji Nakagawa, Hiroaki Inoue,Shohei Ichimaru, Osam Mazda, Toshikazu Kubo
    • Organizer
      ORS 2017 Annual Meeting
    • Place of Presentation
      San Diego Convention Center, CA, USA
    • Year and Date
      2017-03-20
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Regulation of inflammatory cytokine expression and osteoclastgenesis by gap junctional protein in vitro and in vivo2017

    • Author(s)
      Shimomura S, Tsuchida S, Arai Y, Nakagawa S, Inoue H, Ichimaru S, Fujii Y, Mazda O, Kubo T
    • Organizer
      The 5th annual meeting of the international cytokine and interferon society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 軟骨再生プロジェクト

    • URL

      http://www.f.kpu-m.ac.jp/k/orthoped/study/nankotsu.html

    • Related Report
      2018 Annual Research Report 2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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