Exercise protects against cardiac and skeletal muscle dysfunction in a mouse model of inflammatory arthritis

Rheumatoid arthritis (RA) is a systemic inflammatory arthritis impacting joints as well as cardiac and skeletal muscle. RA's distinct impact on cardiac and skeletal muscle tissue is suggested by studies showing that new RA pharmacologic agents strongly improve joint inflammation, but have little impact on RA associated mortality, cardiovascular disease and sarcopenia. Thus, the objective is to understand the distinct effects of RA on cardiac and skeletal muscle, and to therapeutically target these tissues through endurance-based exercise as a way to improve RA mortality and morbidity. Methods We utilize the well characterized RA mouse model, the K/BxN mouse to investigate cardiac and skeletal muscle pathologies, including the use of wheel running exercise to mitigate these pathologies. Results Strikingly, we found that K/BxN mice, like human RA patients, also exhibit both cardiac and skeletal muscle myopathies that were correlated with circulating IL-6 levels. Three months of wheel running exercise significantly improved K/BxN joint swelling and reduced systemic IL-6 concentrations. Importantly, there were morphologic, gene expression and functional improvements in both the skeletal muscle and cardiac myopathies with exercise. Conclusion The K/BxN mouse model of RA recapitulated important RA clinical comorbidities, including altered joint, cardiac and skeletal muscle function. These morphological, molecular and functional alterations were mitigated with regular exercise, thus suggesting exercise as a potential therapeutic intervention to lessen disease activity in the joint and the peripheral tissues, including the heart and skeletal muscle.