Yan Xu, Fu Su, Xie Ying, Zhang Chunlin, Wu Xuejian
Department of orthopaedics, The first affiliated hospital of Zhengzhou University, Zhengzhou, China.
Department of blood transfusion, The first affiliated hospital of Zhengzhou University, Zhengzhou, China.
Biomol Biomed. 2025 Mar 7;25(4):905-913. doi: 10.17305/bb.2024.11156.
Osteoarthritis (OA) is a prevalent degenerative disease characterized by pain and cartilage damage in its later stages, while early OA is marked by the loss of cartilage's mechanical function. Recent studies suggest that Piezo1, a mechanotransducer, may contribute to cartilage degradation under abnormal physical stress. This study investigates the mechanism by which Piezo1 mediates the loss of cartilage's mechanical properties. Using rat chondrocytes cultured in a 3D in vitro model, we found that fluid flow-induced physical stress activates constitutively expressed Piezo1, leading to increased catabolic activity and apoptosis, which, in turn, disrupts the matrix structure. Ex vivo cartilage experiments further demonstrated that the mechanical stress-induced loss of cartilage's physical properties (approximately 10% reduction in relaxation modulus) is mediated by Piezo1 and depends on cell viability. Notably, Piezo1 agonists alone did not alter the mechanical behavior of cartilage tissue. In vivo, using an OA rat model induced by anterior cruciate ligament transection, we observed cartilage integrity degradation and loss of mechanical properties, which were partially mitigated by Piezo1 inhibition. RNA sequencing revealed significant modulation of the PI3K signaling and matrix regulation pathways. Collectively, this study demonstrates that Piezo1-mediated catabolic activity in chondrocytes is a key driver of the loss of cartilage's mechanical function during the relaxation phase.
骨关节炎（OA）是一种常见的退行性疾病，其晚期特征为疼痛和软骨损伤，而早期OA则以软骨机械功能丧失为标志。最近的研究表明，机械力感受器Piezo1可能在异常物理应力下导致软骨降解。本研究探讨了Piezo1介导软骨机械性能丧失的机制。利用在三维体外模型中培养的大鼠软骨细胞，我们发现流体流动诱导的物理应力激活了组成性表达的Piezo1，导致分解代谢活性增加和细胞凋亡，进而破坏了基质结构。体外软骨实验进一步证明，机械应力诱导的软骨物理性能丧失（松弛模量降低约10%）由Piezo1介导，并依赖于细胞活力。值得注意的是，单独使用Piezo1激动剂并不会改变软骨组织的力学行为。在体内，使用前交叉韧带横断诱导的OA大鼠模型，我们观察到软骨完整性降解和力学性能丧失，Piezo1抑制可部分缓解这些情况。RNA测序显示PI3K信号通路和基质调节通路有显著调节。总的来说，本研究表明，Piezo1介导的软骨细胞分解代谢活性是松弛期软骨机械功能丧失的关键驱动因素。
