Development of exercise therapy for rheumatoid arthritis by controlling hypoxia-inducible factor

• Project/Area Number: 18K10752
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59010:Rehabilitation science-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Shuji Nakagawa 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30643382)
• Co-Investigator(Kenkyū-buntansha): 新井 祐志 京都府立医科大学, 医学(系)研究科(研究院), 准教授 (50347449)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 関節リウマチ / 運動療法 / サルコペニア / 低酸素

Outline of Final Research Achievements

The effects of exercise therapy for rheumatoid arthritis on joint destruction and sarcopenia were investigated. Animal models of arthritis were subjected to mild treadmill running, and the degree of joint destruction, inflammation, and muscle atrophy in the periprosthetic muscles of the lower limb were evaluated. In the arthritis model, treadmill running suppressed joint destruction and inflammatory factors such as TNF-α and Conexin43. The lower extremity muscles showed marked atrophy and fibrosis in the natural course of the arthritic model, whereas atrophy and fibrosis were mild in the treadmill group.

Academic Significance and Societal Importance of the Research Achievements

関節リウマチ患者に対する運動療法は関節破壊を助長する可能性があるためこれまで積極的に日常診療では行われてこなかった。本研究では適切な時期にmildな負荷量であるトレッドミル走行を行うことで関節破壊や筋萎縮を改善させる効果が明らかにした。関節リウマチに対する治療として薬物療法に加えて運動療法を併用して行うことで安全かつ効率的に治療効果を高める可能性を示したことが本研究の意義と考える。

Research Products

• [Journal Article] Sustained Hypoxia Suppresses Joint Destruction in a Rat Model of Rheumatoid Arthritis via Negative Feedback of Hypoxia Inducible Factor-1α (2021)
  • Author(s): Kaihara Kenta、Nakagawa Shuji、Arai Yuji、Inoue Hiroaki、Tsuchida Shinji、Fujii Yuta、Kamada Yoichiro、Kishida Tsunao、Mazda Osam、Takahashi Kenji
  • Journal Title: International Journal of Molecular Sciences Volume: 22 Issue: 8 Pages: 3898-3898
  • DOI: 10.3390/ijms22083898
  • Peer Reviewed / Open Access
• [Journal Article] Clinical outcomes after medial patellofemoral ligament reconstruction: an analysis of changes in the patellofemoral joint alignment (2020)
  • Author(s): Fujii Yuta、Nakagawa Shuji、Arai Yuji、Inoue Hiroaki、Kan Hiroyuki、Hino Manabu、Kaihara Kenta、Mikami Yasuo
  • Journal Title: International Orthopaedics Volume: - Issue: 5 Pages: 1215-1222
  • DOI: 10.1007/s00264-020-04765-w
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Relationship of alignment in the lower extremity with early degeneration of articular cartilage after resection of the medial meniscus (2020)
  • Author(s): Nakagawa Shuji、Arai Yuji、Inoue Hiroaki、Fujii Yuta、Kaihara Kenta、Mikami Yasuo
  • Journal Title: Medicine Volume: 99 Issue: 44 Pages: e22984-e22984
  • DOI: 10.1097/md.0000000000022984
  • Peer Reviewed / Open Access / Int'l Joint Research
• [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
  • Peer Reviewed / Open Access
• [Presentation] Analysis of muscle atrophy and fibrosis in fast and slow muscles in a rat model of arthritis (2021)
  • Author(s): Kamada Y, Toyama S, Inoue H, Nakagawa S, Fujii Y, Kaihara K, Arai Y, Mazda O, Takahashi K
  • Organizer: 2021 ORS annual meeting
  • Int'l Joint Research
• [Presentation] Influence of heat stress on SIRT1 transfected chondrocytes (2021)
  • Author(s): Kaihara K, Inoue H, Nakagawa S, Arai Y, Fujii Y, Kamada Y, Mazda O, Takahashi K
  • Organizer: 2021 OARSI annual meeting
  • Int'l Joint Research
• [Presentation] Treadmill running suppressed joint destruction in a rheumatoid arthritis rat model (2020)
  • Author(s): Fujii Y, Inoue H, Arai Y, Shimomura S, Nakagawa S, Tsuchida S, Kamada Y, Kaihara K, Mazda O, Mikami Y
  • Organizer: 66th Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] Effect of hif-1α stabilization by deferoxamine on chondrocyte and articular cartilage (2020)
  • Author(s): Kaihara K, Nakagawa S, Arai Y, Fujii Y, Inoue H, Tsuchida S, Kamada Y, Mazda O, Mikami Y
  • Organizer: 66th Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] Analysis of reaction to tensile stress in chondrocytes in hypoxic environment (2020)
  • Author(s): Kamada Y, Inoue H, Arai Y, Shimomura S, Nakagawa S, Tsuchida S, Fujii Y, Kaihara K, Mazda O, Mikami Y
  • Organizer: 66th Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] Treadmill Running Suppressed Joint Destruction In A Rheumatoid Arthritis Rat Model (2020)
  • Author(s): Yuta Fujii; Hiroaki Inoue; Yuji Arai; Seiji Shimomura; Shuji Nakagawa; Shinji Tsuchida; Yoichiro Kamada; Kenta Kaihara; Osam Mazda; Yasuo Mikami
  • Organizer: 2020 Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research
• [Presentation] トレッドミル走行がラット関節炎モデルの足関節に与える組織学的影響 (2019)
  • Author(s): 藤井雄太，井上裕章，新井祐志，下村征史，中川周士，土田真嗣，鎌田陽一郎，貝原健太，松田 修，久保俊一
  • Organizer: 第34回日本整形外科学会基礎学術集会
• [Presentation] Treadmill Running Ameliorates Articular Cartilage Destruction and Synovitis Histologically in a Rheumatoid Arthritis Rat Model (2019)
  • Author(s): Fujii Y, Inoue H, Arai Y, Shimomura S, Nakagawa S, Tsuchida S, Ichimaru S, Mazda O, Kubo T
  • Organizer: 65th Annual Meeting of Orthopaedic Research Society
  • Int'l Joint Research