Effectiveness of low-intensity exercise in mitigating active arthritis exacerbation in a mouse rheumatoid-arthritis model

Objective To investigate the effects of low-intensity exercise on active arthritis in a 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. Overall design: Low-intensity treadmill exercise was performed after inducing arthritis in SKG/Jcl model mice. The results were compared between the sedentary group (PBS administration), the arthritis group (Mannan 20 mg), and the arthritis + exercise group (Mannan 20 mg + Treadmill), and showed that low-intensity treadmill exercise had an inhibitory effect on arthritis exacerbation.