Li Zilin, Han Lizhi, Wang Bo, Wang Ping, Wang Yuxi, Wang Ruoyu, Lv Xiao, Feng Yong
Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Department of Orthopedics, The First Affiliated Hospital of Bengbu Medical University, Anhui Key Laboratory of Tissue Transformation, Bengbu Medical University, Bengbu, 233000, Anhui Province, China.
J Orthop Translat. 2025 Mar 19;51:278-289. doi: 10.1016/j.jot.2025.01.008. eCollection 2025 Mar.
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.
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.
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.
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.
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.
糖皮质激素性股骨头坏死（SONFH）仍是一个重大的全球健康问题，其发病机制尚不清楚。骨内压升高被认为是SONFH发生的关键起始因素。成骨和血管生成受损被认为在SONFH进展中起关键作用。Piezo1是一种机械敏感阳离子通道，可能感知骨内压的变化。在本研究中，我们旨在探讨Piezo1在SONFH中的作用以及如何靶向Piezo1治疗SONFH。
收集股骨头坏死和股骨颈骨折患者的股骨头组织标本。进行组织学染色、蛋白质印迹法和逆转录聚合酶链反应分析，以研究大鼠模型中骨内压升高与SONFH之间的关系。对股骨头组织进行免疫荧光染色，以研究骨内压升高与血管生成、成骨及SONFH发展之间的时空关系。
在SONFH早期，骨内压升高促进血管生成和成骨。然而，随着压力持续升高，这两个过程均受到抑制。此外，骨内压升高激活了骨髓干细胞中的Piezo1信号通路。Piezo1激活导致细胞内钙内流增加，从而通过钙调神经磷酸酶-活化T细胞核因子1信号通路增强成骨和血管生成。
在SONFH早期，骨髓间充质干细胞中的Piezo1感知骨内压升高，促进血管生成和成骨。靶向Piezo1以促进干细胞的成骨和血管生成潜能，这可以抑制压力进一步升高，有助于SONFH的早期治疗。
目前，骨内压升高对股骨头坏死影响的许多机制仍处于基础理论研究阶段，我们希望尽快将其转化为临床应用。我们发现靶向Piezo1可抑制骨内压进一步升高，减轻糖皮质激素对干细胞和血管的损伤作用，这对早期SONFH的治疗具有重要意义。
