Abstract
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.
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Funding
This work was supported by the [Key Science and Technology Program of Shaanxi Province] under Grant[2021SF-251, 2022SF-345]; and [New talents of Shaanxi Provincial People’s Hospital] under Grant[2021BJ-24].
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Feng, M., Zhang, R., Zhang, M. et al. Administration of necrostatin-1 ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats. J Mol Histol 54, 207–216 (2023). https://doi.org/10.1007/s10735-023-10124-x
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DOI: https://doi.org/10.1007/s10735-023-10124-x