The role of Piezo1 in bone marrow stem cells in response to elevated intraosseous pressure on regulating osteogenesis and angiogenesis of steroid-induced osteonecrosis of the femoral head

Objectives: Steroid-induced osteonecrosis of the femoral head (SONFH) remains a significant global health issue, with an unclear pathogenesis. Elevated intraosseous pressure is considered a key initiating factor in SONFH development. Impaired osteogenesis and angiogenesis are believed to be critical in SONFH progression. Piezo1, a mechanosensitive cation channel, may sense changes in intraosseous pressure. In this study, we set out to explore the role of Piezo1 in SONFH and how to target Piezo1 to treat SONFH. Methods: Femoral head tissue specimens were collected from patients with ONFH and femoral neck fracture. Histological staining, Western blotting, and RT-PCR analysis were conducted to investigate the relationship between elevated intraosseous pressure and SONFH in rat models. Immunofluorescence staining of femoral head tissues was performed to study the spatiotemporal relationship between elevated intraosseous pressure and angiogenesis, osteogenesis, and development of SONFH. Results: In the early stages of SONFH, elevated intraosseous pressure increased angiogenesis and osteogenesis. However, as the pressure continued to rise, both processes were inhibited. Furthermore, Elevated intraosseous pressure activated the Piezo1 signaling pathway in bone marrow stem cells. Piezo1 activation led to increased intracellular calcium influx, thus enhancing osteogenesis and angiogenesis through CAM-NFAT1 signaling pathway. Conclusion: In the early stages of SONFH, Piezo1 in BMSCs senses increased intraosseous pressure, promoting angiogenesis and osteogenesis. Targeting Piezo1 to promote the osteogenic and angiogenic potential of stem cells, which could curb further increases in pressure, contribute to early treatment of SONFH. The translational potential of this article: Currently, many mechanisms of the impact of elevated intraosseous pressure on osteonecrosis of the femoral head are still in the basic theoretical research stage, and we hope to translate them into clinical applications as soon as possible. We discovered that targeting Piezo1 curb further increases in intraosseous pressure, alleviating the damaging effects of glucocorticoids on stem cells and blood vessels, which exerting great significance in treatment of early stage SONFH.