Mechanical cues enhance chondrocyte function: Insights from mechanoreception, regulation, and biological responses.

Chondrocytes, the sole cell type in articular cartilage, are responsible for synthesizing and maintaining the primary components of the extracellular matrix (ECM). In daily life, chondrocytes are subjected to diverse mechanical stimuli, and the mechanoregulation of their biological responses plays a crucial role in cartilage function. Chondrocytes exhibit remarkable mechanoadaptation, as mechanical stimulation effectively promotes their homeostasis, development, and regeneration-critical factors for regenerative medicine. Thus, a deeper understanding of chondrocyte mechanosensing mechanism is essential. A key challenge lies in the significant biomechanical heterogeneity of chondrocytes across developmental stages and spatial locations of articular cartilage, leading to variations in their mechanosensing and mechanoresponsive behaviors. Elucidating the spatiotemporal biomechanical properties of chondrocytes is of great importance. Mechanical cues regulate chondrocyte homeostasis through multidimensional mechanisms, enhance energy metabolism, and dynamically couple with the cytoskeleton to optimize their responsiveness to matrix mechanical microenvironment. However, under pathological conditions, the aberrant mechanosensing of chondrocyte exacerbates inflammatory responses and matrix degradation, which further deteriorating the mechanical microenvironment. Growing evidence has indicated that some critical factors include dysregulated activation of mechanosensitive ion channels, disrupted integrin signaling pathways, and structural damage to primary cilia induce abnormal chondrocyte function. Biomechanical intervention strategies, such as mechanical loading techniques and exercise-based rehabilitation, hold promising potential for cartilage repair and regeneration by reconstructing the physiological-related mechanical microenvironment. This review provides a theoretical foundation for understanding the mechanisms of cartilage degenerative diseases and developing targeted therapies from a mechanobiological perspective.