High fluid shear stress induces Hippo/YAP pathway in articular cartilage superficial layer cells: a potential mechanistic link to 0steoarthritis. 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. Overall design: The Primary articular cartilage superficial layer cells were treated with or without 20 dyne/cm² fluid shear stress

异常机械负荷是骨关节炎（Osteoarthritis, OA）发病的重要诱因，可导致关节软骨损伤。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影响及其潜在作用机制。研究发现，20 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变化。YAP（Yes相关蛋白）在介导高流体切应力的生物学效应中发挥关键作用，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切断术（Anterior Cruciate Ligament Transection, ACLT）或碘乙酸钠（Monosodium iodoacetate, MIA）注射构建骨关节炎模型，以进一步验证上述研究发现。总体实验设计：对原代关节软骨表层细胞施加或不施加20 dyne/cm²的流体切应力。