Day Jessica, Louis Cynthia, Swiderski Kristy, Stock Angus, Wong Huon, Yao Wentao, Liu Bonnia, Nadesapillai Suba, Lynch Gordon S, Wicks Ian P
Inflammation Division, The Walter and Eliza Hall Institute of Medical Research, Victoria, Australia.
Department of Medical Biology, The University of Melbourne, Victoria, Australia.
JCI Insight. 2025 Mar 4;10(7):e179928. doi: 10.1172/jci.insight.179928.
The deleterious consequences of chronic synovitis on cartilage, tendon, and bone in rheumatoid arthritis (RA) are well described. In contrast, its effects on periarticular skeletal muscle are under-studied. Furthermore, while TNF inhibition is an effective therapy for RA synovitis, it exacerbates fibrosis in muscle injury models. We aimed to investigate whether myositis and muscle fibrosis are features of inflammatory arthritis and evaluate whether targeted RA therapies influence these disease features. Periarticular muscle was analyzed in murine models of poly- and monoarticular inflammatory arthritis: serum transfer-induced arthritis, collagen-induced arthritis, K/BxN, and antigen-induced arthritis (AIA). Periarticular myositis and an increase in muscle fibroadipocyte progenitors (FAPs) were observed in all models, despite diverse arthritogenic mechanisms. Periarticular muscle fibrosis was observed from day 15 in AIA. Neither etanercept nor baricitinib suppressed periarticular myositis or subsequent fibrosis compared to vehicle, despite reducing arthritis. Notably, etanercept failed to prevent muscle fibrosis even when initiated early, but this was not linked to increased FAP survival or collagen production. Corroborating these data, radiographic and histological analyses revealed periarticular myositis in patients with RA. We conclude that periarticular myositis and fibrosis are under-recognized features of inflammatory arthritis. Targeted RA therapies may not prevent periarticular muscle sequelae, despite controlling arthritis.
类风湿关节炎（RA）中慢性滑膜炎对软骨、肌腱和骨骼的有害影响已有充分描述。相比之下，其对关节周围骨骼肌的影响研究不足。此外，虽然肿瘤坏死因子（TNF）抑制是治疗RA滑膜炎的有效方法，但在肌肉损伤模型中会加剧纤维化。我们旨在研究肌炎和肌肉纤维化是否为炎性关节炎的特征，并评估靶向性RA疗法是否会影响这些疾病特征。在多关节和单关节炎性关节炎的小鼠模型中分析关节周围肌肉：血清转移诱导性关节炎、胶原诱导性关节炎、K/BxN和抗原诱导性关节炎（AIA）。尽管致关节炎机制不同，但在所有模型中均观察到关节周围肌炎以及肌肉纤维脂肪细胞祖细胞（FAP）增加。在AIA模型中，从第15天开始观察到关节周围肌肉纤维化。与赋形剂相比，依那西普和巴瑞替尼均未抑制关节周围肌炎或随后的纤维化，尽管它们减轻了关节炎症状。值得注意的是，即使早期开始使用依那西普也未能预防肌肉纤维化，但这与FAP存活增加或胶原蛋白生成增加无关。与这些数据一致，影像学和组织学分析显示RA患者存在关节周围肌炎。我们得出结论，关节周围肌炎和纤维化是炎性关节炎中未得到充分认识的特征。尽管能控制关节炎，但靶向性RA疗法可能无法预防关节周围肌肉后遗症。
