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.

中文翻译：

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运动可预防炎症性关节炎小鼠模型中的心脏和骨骼肌功能障碍

类风湿性关节炎 (RA) 是一种影响关节以及心肌和骨骼肌的全身性炎症性关节炎。研究表明 RA 对心脏和骨骼肌组织的独特影响表明，新的 RA 药物可显着改善关节炎症，但对 RA 相关死亡率、心血管疾病和肌肉减少症几乎没有影响。因此，目标是了解 RA 对心肌和骨骼肌的独特影响，并通过基于耐力的运动来治疗这些组织，以此作为提高 RA 死亡率和发病率的一种方式。方法 我们利用充分表征的 RA 小鼠模型 K/BxN 小鼠来研究心脏和骨骼肌病变，包括使用轮式跑步运动来减轻这些病变。结果 引人注目的是，我们发现 K/BxN 小鼠，像人类 RA 患者一样，也表现出与循环 IL-6 水平相关的心脏和骨骼肌肌病。三个月的轮式跑步运动显着改善了 K/BxN 关节肿胀并降低了全身 IL-6 浓度。重要的是，运动后骨骼肌和心肌病的形态、基因表达和功能都有所改善。结论 K/BxN RA 小鼠模型概括了重要的 RA 临床合并症，包括关节、心脏和骨骼肌功能的改变。这些形态、分子和功能的改变通过定期运动得到缓解，因此表明运动是一种潜在的治疗干预措施，可以减少关节和外周组织（包括心脏和骨骼肌）的疾病活动。还表现出与循环 IL-6 水平相关的心脏和骨骼肌肌病。三个月的轮式跑步运动显着改善了 K/BxN 关节肿胀并降低了全身 IL-6 浓度。重要的是，运动后骨骼肌和心肌病的形态、基因表达和功能都有所改善。结论 K/BxN RA 小鼠模型概括了重要的 RA 临床合并症，包括关节、心脏和骨骼肌功能的改变。这些形态、分子和功能的改变通过定期运动得到缓解，因此表明运动是一种潜在的治疗干预措施，可以减少关节和外周组织（包括心脏和骨骼肌）的疾病活动。还表现出与循环 IL-6 水平相关的心脏和骨骼肌肌病。三个月的轮式跑步运动显着改善了 K/BxN 关节肿胀并降低了全身 IL-6 浓度。重要的是，运动后骨骼肌和心肌病的形态、基因表达和功能都有所改善。结论 K/BxN RA 小鼠模型概括了重要的 RA 临床合并症，包括关节、心脏和骨骼肌功能的改变。这些形态、分子和功能的改变通过定期运动得到缓解，因此表明运动是一种潜在的治疗干预措施，可以减少关节和外周组织（包括心脏和骨骼肌）的疾病活动。