NFATc1 Mediates LIPUS-Induced Osteoblast Differentiation through P2X7 in MC3T3-E1 Cells

Low-intensity pulsed ultrasound (LIPUS) is primarily used to treatment fractures in orthopedics. Several previous studies have shown that the P2X7 receptor plays a crucial role in the response to osteogenesis induced by mechanical stimulation, which is regulated by the nuclear factor of activated T cells c1 (NFATc1), an essential mediator. However, the effects of LIPUS, a mechanical stimulator, on the regulation of NFATc1 during osteogenesis have not been elucidated. In this study, we investigated the roles of the P2X7 receptor and NFATc1 in LIPUS-induced bone formation. LIPUS induces the expression of osteogenesis-related transcription factors, extracellular matrix proteins, and Ca2+ via the P2X7-NFATc1 pathway. These findings provide the first demonstration that LIPUS drives bone formation by activating P2X7-NFATc1 in osteoblasts.