Role of the RA system in disuse joint contracture: a new strategy to maintain ADLs in the elderly

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07485
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• Research Institution: Morinomiya University of Medical Sciences
• Principal Investigator: Kawahata Hirohisa 森ノ宮医療大学, 保健医療学部, 教授 (30454680)
• Co-Investigator(Kenkyū-buntansha): 青木 元邦 森ノ宮医療大学, 保健医療学部, 教授 (00346214)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 関節拘縮 / 滑膜組織 / 線維化 / レニン・アンギオテンシン(RA)系 / アンギオテンシンII (AngII) / Ang II 1型受容体(AT1R)

Outline of Final Research Achievements

We previously described that the renin-angiotensin (RA) system regulates chondrocyte proliferation and differentiation and that the hypoxia-inducible factor HIF-1α is involved in the synovial fibrosis of joint contractures.
In the present study, we investigated the involvement of the RA system in joint contracture. We observed that angiotensin II type 1 receptor (AT1R)-expressing cells were widely distributed in the fibrotic synovial tissues caused by the development of contractures, and that AT1R gene expression was also enhanced. In addition, Ang II administration resulted in limited range of motion and progressive fibrosis of the synovial tissue. Furthermore, AT1R inhibitor (Olmesartan) administration improved range of motion restriction and fibrosis. These results suggest that the RA system is strongly involved in the pathogenesis of joint contractures.

Free Research Field

実験病理学

Academic Significance and Societal Importance of the Research Achievements

近年の超高齢社会においてロコモティヴシンドロームが注目されているが、関節疾患は関節包の退行性変化による関節拘縮を引き起こすことから、その予防・改善がきわめて重要となる。しかし、現状では温熱療法や運動療法などの対処療法が行われているのみで、病態メカニズムを基盤とした関節機能改善には至っていない。本研究では関節拘縮におけるRA系の関与について検討し、アンギオテンシン（Ang）IIが滑膜組織の線維化と可動域制限を促進することや、Ang II受容体阻害薬はこれらを改善することを示した。この結果は関節拘縮の病態進展へのRA系の関与と、高血圧を有する高齢者に対する関節機能の維持に貢献するものと考える。