Mechanotransduction pathways in the regulation of cartilage chondrocyte homoeostasis

Mechanical stress plays a critical role in cartilage development and homoeostasis. Chondrocytes are surrounded by a narrow pericellular matrix (PCM), which absorbs dynamic and static forces and transmits them to the chondrocyte surface. Recent studies have demonstrated that molecular components, including perlecan, collagen and hyaluronan, provide distinct physical properties for the PCM and maintain the essential microenvironment of chondrocytes. These physical signals are sensed by receptors and molecules located in the cell membrane, such as Ca2+ channels, the primary cilium and integrins, and a series of downstream molecular pathways are involved in mechanotransduction in cartilage. All mechanoreceptors convert outside signals into chemical and biological signals, which then regulate transcription in chondrocytes in response to mechanical stresses. This review highlights recent progress and focuses on the function of the PCM and cell surface molecules in chondrocyte mechanotransduction. Emerging understanding of the cellular and molecular mechanisms that regulate mechanotransduction will provide new insights into osteoarthritis pathogenesis and precision strategies that could be used in its treatment.