Emerging evidence suggests that extracellular vesicles (EVs) can play roles in inflammatory processes and joint degradation in primary osteoarthritis (OA), a common age-associated joint disease. EV subpopulations express tetraspanins and platelet markers that may reflect OA pathogenesis. The present study investigated the associations between these EV surface markers and articular cartilage degradation, subjectively and objectively assessed pain, and functional limitations in primary knee OA (KOA). Serum EVs were determined by high-sensitivity flow cytometry (large CD61+ EVs) and single particle interferometric reflectance imaging sensor (small CD41+, CD63+, CD81+, and CD9+ EVs) from end-stage KOA patients and controls (n = 8 per group). Knee pain and physical functions were assessed with several health- and pain-related questionnaires, established measurements of physical medicine, and neuromuscular examination. The obtained data were analyzed using supervised and unsupervised univariate and multivariate models. With the combined dataset of cartilage thickness, knee function, pain, sensation, and EV molecular signatures, we identified highly correlated groups of variables and found several EV markers that were statistically significant predictors of pain, physical limitations, and other aspects of well-being for KOA patients, for instance CD41+/CD63+/CD9+ small EVs associated with the range of motion of the knee, physical performance, and pain sensitivity. Particular serum EV subpopulations showed clear associations with KOA pain and functional limitations, suggesting that their implications in OA pathophysiology warrant further study.

中文翻译：

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血清细胞外囊泡的四跨膜蛋白谱反映了膝骨关节炎的功能限制和疼痛感知

新的证据表明，细胞外囊泡（EV）可以在原发性骨关节炎（OA）（一种常见的与年龄相关的关节疾病）的炎症过程和关节退化中发挥作用。EV 亚群表达四跨膜蛋白和血小板标记物，可能反映 OA 发病机制。本研究调查了这些 EV 表面标志物与关节软骨退化之间的关联，主观和客观评估了原发性膝关节 OA (KOA) 的疼痛和功能限制。通过高灵敏度流式细胞术（大 CD61+ EV）和单粒子干涉反射成像传感器（小 CD41+、CD63+、CD81+ 和 CD9+ EV）测定终末期 KOA 患者和对照（每组 n = 8）的血清 EV。通过一些健康和疼痛相关的问卷、既定的物理医学测量和神经肌肉检查来评估膝盖疼痛和身体功能。使用有监督和无监督的单变量和多变量模型对获得的数据进行分析。通过软骨厚度、膝关节功能、疼痛、感觉和 EV 分子特征的组合数据集，我们确定了高度相关的变量组，并发现了几种 EV 标记物，这些标记物在统计上对疼痛、身体限制和健康的其他方面具有显着的预测作用对于 KOA 患者，例如 CD41+/CD63+/CD9+ 小 EV 与膝关节活动范围、身体表现和疼痛敏感性相关。特定的血清 EV 亚群显示出与 KOA 疼痛和功能限制明显相关，表明它们在 OA 病理生理学中的影响值得进一步研究。