High fluid shear stress induces Hippo/YAP pathway in articular cartilage superficial layer cells: a potential mechanistic link to 0steoarthritis

Abnormal mechanical loading, which can lead to articular cartilage damage, is a significant contributor to the onset of osteoarthritis (OA). Articular cartilage superficial layer cells are among the first cells to respond to changes in the mechanical environment and are highly sensitive to mechanical stimuli. This study aimed to investigate the effects of high fluid shear stress on the articular cartilage superficial layer cells and the underlying mechanisms. We found that high fluid shear stress of 20 dyne/cm² induces inflammation and promotes catabolic processes in these cells. Short-term high fluid shear stress has a protective effect, but its efficacy varies with time. YAP plays a crucial role in mediating the effects of high fluid shear stress and may represent a potential therapeutic target for early-stage osteoarthritis. The study also established osteoarthritis models using anterior cruciate ligament transection (ACLT) or injection of sodium iodoacetate (MIA) to further confirm the findings.异常机械负荷可引发关节软骨损伤，是骨关节炎（Osteoarthritis, OA）发病的重要诱因。关节软骨表层细胞是最早响应机械环境变化的细胞类群之一，对机械刺激具有高度敏感性。本研究旨在探究高流体切应力对关节软骨表层细胞的作用及其潜在分子机制。研究发现，20达因/平方厘米（dyne/cm²）的高流体切应力可诱导此类细胞产生炎症反应，并促进其分解代谢过程。短期高流体切应力则具有保护作用，但其保护效力随时间推移而发生变化。YAP在介导高流体切应力的生物学效应过程中发挥关键作用，或可成为早期骨关节炎的潜在治疗靶点。本研究还通过前交叉韧带横断术（Anterior Cruciate Ligament Transection, ACLT）或碘乙酸钠（Sodium Iodoacetate, MIA）注射构建骨关节炎模型，以进一步验证上述研究结论。