Effectiveness of Exercise Intervention in Preventing Active Arthritis Exacerbation in an SKG Mouse Model of Rheumatoid Arthritis

Objectives To investigate the effects of low-intensity exercise on active arthritis in an SKG mouse model of human rheumatoid arthritis (RA) pathology. Methods Twenty-four female SKG mice were divided into three groups: ‘sedentary’ (control), ‘AR’ (induced arthritis), and ‘AREx’ (induced arthritis plus low-intensity exercise). Arthritis was induced via intraperitoneal administration of mannan. After a 2-week inflammation period, low-intensity treadmill exercise was performed only in the AREx group. Arthritis was assessed weekly during the rearing period. After 4 weeks of exercise, histological and bone morphometric analyses of the right ankle joint were performed. A histological analysis of the gastrocnemius muscle was also performed. Bulk mRNA sequencing was conducted on the left synovial membrane-fat pad (SM-FP) complex. Results The synovitis score showed no change; however, the arthritis score was significantly lower in the AREx group than in the AR group ( p <0.05), indicating that low-intensity exercise suppressed arthritis exacerbation. The calcaneal and talar bone volumes decreased in the AR group, whereas the AREx group showed no significant change. In the SM-FP 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. Immunohistochemical 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). Conclusion Low-intensity exercise therapy for active RA showed anti-inflammatory and suppressive effects on arthritis exacerbation in SKG mice, a mouse model of human RA pathology. Key messages Exercise had an anti-inflammatory effect on SKG mice, a mouse model of rheumatoid arthritis. Exercise suppresses pro-inflammatory cytokine pathways such as IL6/Jak/Stat3 signalling in the synovial-fat complex tissue. Exercise therapy is effective in improving the pathophysiology of active rheumatoid arthritis.