Mechanical signal transduction are crucial for chondrocyte in response to mechanical cues during the growth, development and osteoarthritis (OA) of articular cartilage. Extracellular matrix (ECM) turnover regulates the matrix mechanical microenvironment of chondrocytes. Thus, understanding the mechanotransduction mechanisms during chondrocyte sensing the matrix mechanical microenvironment can develop effective targeted therapy for OA. In recent decades, growing evidences are rapidly advancing our understanding of the mechanical force-dependent cartilage remodeling and injury responses mediated by TRPV4 and PIEZOs. In this review, we highlighted the mechanosensing mechanism mediated by TRPV4 and PIEZOs during chondrocytes sensing mechanical microenvironment of the ECM. Additionally, the latest progress in the regulation of OA by inflammatory signals mediated by TRPV4 and PIEZOs was also introduced. These recent insights provide the potential mechanotheraputic strategies to target these channels and prevent cartilage degeneration associated with OA. This review will shed light on the pathogenesis of articular cartilage, searching clinical targeted therapies, and designing cell-induced biomaterials.
软骨细胞转导机械力信号的力转导过程在关节软骨生长、发育和骨性关节炎（OA）过程中发挥着重要作用。在关节软骨中，细胞外基质代谢活动调控着软骨细胞的基质力学微环境。因此，理解软骨细胞感受基质力学微环境的力转导机制能够通过精准靶向机械力感受器有效建立OA治疗策略。近十几年，大量研究证实力敏感离子通道TRPV4和PIEZOs在关节软骨细胞中大量表达，而且介导机械力相关的软骨重塑和损伤响应。本文综述了软骨细胞感受基质力学微环境过程中TRPV4和PIEZOs介导的力感受和力响应方面的相关研究，同时也介绍了TRPV4和PIEZOs介导炎症信号调控骨性关节炎方面的进展。本文为理解关节软骨发病机制和寻求可能药物靶点，以及设计细胞诱导性生物材料提供了新思路。.
Keywords: Calcium signaling; Chondrocyte; Matrix microenvironment; Osteoarthritis; PIEZOs; TRPV4.