Molecular mechanisms and therapeutic targets of mechanical stress regulating osteoarthritis

• PIEZO ion channels are critical mechanosensors in osteoarthritis, mediating Ca2+ influx and influencing chondrocyte apoptosis, inflammation, and pain. • Mechanical stress is a core driver of osteoarthritis pathogenesis, with PIEZO channels representing a promising therapeutic target. • Inhibiting PIEZO channels, e.g., with GsMTx4, may alleviate osteoarthritis progression by modulating downstream signaling pathways. • Current research gaps include the need for specific modulators of PIEZO2 and a clearer understanding of downstream signaling networks.