Effectiveness of Low‐Intensity Exercise in Mitigating Active Arthritis Exacerbation in a Mouse Rheumatoid‐Arthritis Model

Rheumatoid arthritis is an autoimmune disease characterized by synovitis, reducing the quality of life of affected individuals through joint swelling and inflammation. Recently, the efficacy of exercise therapy has been proposed for rheumatoid arthritis, but its detailed mechanism is still unclear. Herein, we used a mouse model of human rheumatoid-arthritis pathology to investigate the effects of low-intensity exercise on active arthritis. Twenty-four SKG mice were divided into three groups: "sedentary," "AR" (induced arthritis), and "AREx" (induced arthritis plus low-intensity exercise), with only the AREx group performing treadmill exercise for 4 weeks. During the rearing period, macroscopic arthritis scores were assessed weekly, and histological and bone morphometric analysis of the ankle joints was performed after all interventions. In addition, bulk mRNA sequencing was performed for the synovial-fat pad complex. Consequently, the histological synovitis score showed no change; however, the arthritis score was significantly lower in the AREx group than in the AR group (p < 0.05). The calcaneal and talar bone volumes decreased in the AR group, whereas the AREx group showed no significant change. In the synovial-fat pad complex tissue, the gene expression of inflammatory cytokines decreased in the AREx group compared with the AR group, particularly the suppression of IL6/Jak/Stat3. IHC analysis revealed significantly decreased expression of pro-inflammatory cytokines and increased expression of anti-inflammatory cytokines in the synovium of the AREx group compared with the AR group (p < 0.05). In summary, low-intensity exercise therapy for active rheumatoid arthritis was suggested to have anti-inflammatory effects and to mitigate arthritis exacerbation.