Glucocorticoid (GC)-induced osteonecrosis of the femoral head (ONFH) is a serious complication of glucocorticoid treatment and is characterized by dysfunctional bone reconstruction at necrotic sites. Our previous study confirmed the protective potential of necrostatin-1, a selective blocker of necroptosis, in glucocorticoid-induced osteoporosis. In this study, rat models of GC-induced ONFH were established to evaluate the effects of necrostatin-1 on osteonecrotic changes and repair processes. Osteonecrosis was verified by histopathological staining. An analysis of trabecular bone architecture was performed to evaluate osteogenesis in the osteonecrotic zone. Then, necroptotic signaling molecules such as RIP1 and RIP3 were examined by immunohistochemistry. Histopathological observations indicated that necrostatin-1 administration reduced the incidence of osteonecrosis and the osteogenic response in subchondral areas. Additionally, bone histomorphometry demonstrated that necrostatin-1 intervention could restore bone reconstruction in the necrotic zone. The protective mechanism of necrostatin-1 was related to the inhibition of RIP1 and RIP3. Necrostatin-1 administration alleviated GC-induced ONFH in rats by attenuating the formation of necrotic lesions, recovering the function of osteogenesis, and suppressing glucocorticoid-induced osteocytic necroptosis by inhibiting the expression of RIP1 and RIP3.

糖皮质激素 (GC) 诱导的股骨头坏死 (ONFH) 是糖皮质激素治疗的严重并发症，其特征是坏死部位的骨重建功能失调。我们之前的研究证实了 necrostatin-1（一种坏死性凋亡的选择性阻断剂）在糖皮质激素诱导的骨质疏松症中的保护潜力。在本研究中，建立了 GC 诱导的 ONFH 大鼠模型，以评估 necrostatin-1 对骨坏死变化和修复过程的影响。通过组织病理学染色证实骨坏死。对骨小梁结构进行了分析，以评估骨坏死区的成骨作用。然后，通过免疫组织化学检查 RIP1 和 RIP3 等坏死信号分子。组织病理学观察表明，施用 necrostatin-1 可降低骨坏死的发生率和软骨下区域的成骨反应。此外，骨组织形态学表明，necrostatin-1 干预可以恢复坏死区的骨重建。necrostatin-1的保护机制与抑制RIP1和RIP3有关。Necrostatin-1 给药通过减弱坏死病变的形成、恢复成骨功能和通过抑制 RIP1 和 RIP3 的表达抑制糖皮质激素诱导的骨细胞坏死性凋亡来减轻 GC 诱导的大鼠 ONFH。necrostatin-1的保护机制与抑制RIP1和RIP3有关。Necrostatin-1 给药通过减弱坏死病变的形成、恢复成骨功能和通过抑制 RIP1 和 RIP3 的表达抑制糖皮质激素诱导的骨细胞坏死性凋亡来减轻 GC 诱导的大鼠 ONFH。necrostatin-1的保护机制与抑制RIP1和RIP3有关。Necrostatin-1 给药通过减弱坏死病变的形成、恢复成骨功能和通过抑制 RIP1 和 RIP3 的表达抑制糖皮质激素诱导的骨细胞坏死性凋亡来减轻 GC 诱导的大鼠 ONFH。