Piezo1-mediated mechanotransduction in bone formation and fracture repair

The mechanosensitive ion channel Piezo1 is a crucial transducer of mechanical forces into biological signals governing skeletal development and fracture repair. This review summarizes its central role in bone formation, primarily through endochondral ossification. We detail how Piezo1 regulates key processes including chondrocytes-to-osteoblasts transdifferentiation, osteogenic fate determination in skeletal stem/progenitor cells, and functional activation of mature osteoblasts. Evidence from genetic models demonstrates that Piezo1 deficiency in these cell lineages leads to profound skeletal defects and fragility. Furthermore, Piezo1 is essential for fracture healing, coordinating periosteal stem cell activity, chondrocyte fate and macrophages regulation within the repair callus to enable successful bone regeneration. Finally, we discuss emerging Piezo1-targeted therapeutic strategies, such as low-intensity pulsed ultrasound, biomaterial-based and pharmacological approaches, highlighting its potential as a novel target for treating bone disorders and enhancing fracture repair.