OBJECTIVE Quadriceps muscle weakness is common in knee osteoarthritis (OA). While pain, disuse, and atrophy are commonly cited causes for muscle weakness in OA, emerging evidence suggests changes in muscle quality also occur. Alterations in muscle quality are not well understood, but likely include both cellular and morphologic adaptions. The purpose of this study was to conduct the first cellular-level analysis of the vastus lateralis in adults with moderate knee OA. METHODS Vastus lateralis biopsies were obtained from 24 subjects with moderate knee OA and 15 healthy controls. Quadriceps strength, muscle fiber cross sectional area (CSA), fiber type distribution, extracellular matrix (ECM) content, satellite cell abundance, and profibrotic gene expression were assessed. RESULTS Relative to controls, quadriceps strength was significantly lower in OA subjects (OA 62.23, 50.67-73.8 Nm vs 91.46, 75.91-107.0 Nm, P = 0.003) despite no difference in fiber CSA. OA subjects had significantly fewer Type I fibers (OA 41.51, 35.56-47.47% vs 53.07, 44.86-61.29%, P = 0.022) and more hybrid IIa/x fibers (OA 24.61, 20.61-28.61% vs 16.4, 11.60-21.20%, P = 0.009). Significantly greater ECM content, lower satellite cell density, and higher profibrotic gene expression was observed with OA, and muscle collagen content was inversely correlated to strength and satellite cell (SC) density. CONCLUSION Lower quadriceps function with moderate OA may not result from fiber size impairments, but is associated with ECM expansion. Impaired satellite cell density, high profibrotic gene expression, and a slow-to-fast fiber type transition may contribute to reduced muscle quality in OA. These findings can help guide therapeutic interventions to enhance muscle function with OA.

中文翻译：

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中度膝关节骨关节炎成人股四头肌细胞和分子特性的改变

目的 股四头肌肌无力在膝骨关节炎 (OA) 中很常见。虽然疼痛、废用和萎缩是 OA 肌肉无力的常见原因，但新出现的证据表明肌肉质量也会发生变化。肌肉质量的变化尚不清楚，但可能包括细胞和形态适应。本研究的目的是对中度膝关节 OA 成人股外侧肌进行首次细胞水平分析。方法 从 24 名患有中度膝关节 OA 的受试者和 15 名健康对照者中获得外侧肌活检。评估了股四头肌力量、肌纤维横截面积 (CSA)、纤维类型分布、细胞外基质 (ECM) 含量、卫星细胞丰度和促纤维化基因表达。结果 相对于对照，尽管纤维 CSA 没有差异，OA 受试者的股四头肌力量显着降低（OA 62.23, 50.67-73.8 Nm vs 91.46, 75.91-107.0 Nm，P = 0.003）。OA 受试者的 I 型纤维明显较少（OA 41.51, 35.56-47.47% vs 53.07, 44.86-61.29%, P = 0.022）和更多的混合 IIa/x 纤维（OA 24.61, 20.61-28.64%, 116.07% vs 116.07%） , P = 0.009)。在 OA 中观察到显着更高的 ECM 含量、更低的卫星细胞密度和更高的促纤维化基因表达，并且肌肉胶原蛋白含量与强度和卫星细胞 (SC) 密度呈负相关。结论 中度 OA 的下股四头肌功能可能不是由纤维尺寸损伤引起的，而是与 ECM 扩张有关。卫星细胞密度受损，高促纤维化基因表达，由慢到快的纤维类型转变可能导致 OA 肌肉质量下降。这些发现可以帮助指导治疗干预以增强 OA 的肌肉功能。