Novel therapeutic approaches for rheumatoid arthritis through regulation of gap junction proteins and exercise therapy

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K11214
• 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: Tsuchida Shinji 京都府立医科大学, 医学(系)研究科(研究院), 助教 (10719834)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ギャップ結合 / コネキシン / 関節リウマチ / 運動療法 / リハビリテーション治療

Outline of Final Research Achievements

We assessed the differences in the efficasy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used , and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity.

Free Research Field

関節リウマチ

Academic Significance and Societal Importance of the Research Achievements

研究代表者らはCx43が滑膜におけるTNF-α．IL-6，IL-1βなど炎症性サイトカインを介して関節破壊を誘導することを明らかにしてきた．しかしRAにおいて運動負荷におけるCx43の発現動態は不明であった．本研究でRA動物モデルにおいて一定の運動療法により滑膜内におけるCx43の産生を抑制し，TNF-αの発現を抑制した．また，関節炎期における運動療法によりcathepsin K陽性細胞は減少し，骨形態評価で骨破壊を抑制する効果も明らかにした．臨床上，RA患者の関節炎を経時的に評価し運動療法の施行時期や負荷量を決定することで，Cx43の発現を制御しながら効率的な治療を施行できる可能性がある．