The role of PIEZO ion channels in the musculoskeletal system

PIEZO1 and PIEZO2 are mechanosensitive cation channels that are highly expressed in numerous tissues throughout the body and exhibit diverse, cell-specific functions in multiple organ systems. Within the musculoskeletal system, PIEZO1 functions to maintain mus-cle and bone mass, sense tendon stretch, and regulate senescence and apoptosis in response to mechanical stimuli within cartilage and the intervertebral disc. PIEZO2 is essential for transducing pain and touch sensations as well as proprioception in the nervous system, which can affect musculoskeletal health. PIEZO1 and PIEZO2 have been shown to act both independently as well as synergis-tically in different cell types. Conditions that alter PIEZO channel mechanosensitivity, such as inflammation or genetic mutations, can have drastic effects on these functions. For this reason, therapeutic approaches for PIEZO-related disease focus on altering PIEZO1 and/or PIEZO2 activity in a controlled manner, either through inhibition with small molecules, or through dietary control and supple-mentation to maintain a healthy cell membrane composition. Although many opportunities to better understand PIEZO1 and PIEZO2 remain, the studies summarized in this review highlight how crucial PIEZO channels are to musculoskeletal health and point to prom-ising possible avenues for their modulation as a therapeutic target.

Automated summary

PIEZO1 and PIEZO2 are highly expressed mechanosensitive channels with diverse functions in various tissues. They play important roles in musculoskeletal health, including maintenance of muscle and bone mass, sensing tendon stretch, and regulation of senescence and apoptosis. PIEZO2 is essential for pain and touch perception as well as proprioception. Alterations in PIEZO channel mechanosensitivity can significantly affect these functions. Therapeutic approaches focus on controlling PIEZO1 and/or PIEZO2 activity through inhibition or dietary control. Overall, these studies highlight the crucial role of PIEZO channels in musculoskeletal health and suggest promising avenues for therapeutic modulation.