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Articular cartilage and their chondrocytes are physiologically submitted to diverse types of mechanical cues. Chondrocytes produce and maintain the cartilage by sensing and responding to changing mechanical loads. TRPV4 and PIEZOs, activated by mechanical cues, are important mechanosensing molecules of chondrocytes and have pivotal roles in articular cartilage during health and disease. The objective of this review is to introduce the recent progress indicating that the mechanosensitive ion channels, TRPV4 and PIEZOs, are involved in the chondrocyte sensing of mechanical and inflammatory cues. We present a focus on the important role of TRPV4 and PIEZOs in the mechanotransduction regulating diverse chondrocyte functions in the biomechanical microenvironment. The review synthesizes the most recent advances in our understanding of how mechanical stimuli affect various cellular behaviors and functions through differentially activating TRPV4 and PIEZO ion channels in chondrocyte. Advances in understanding the complex roles of TRPV4/PIEZO-mediated mechanosignaling mechanisms have the potential to recapitulate physiological biomechanical microenvironments and design cell-instructive biomaterials for cartilage tissue engineering.

TRPV4 and PIEZO Channels Mediate the Mechanosensing of Chondrocytes to the Biomechanical Microenvironment