Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun;54(3):207-216.
doi: 10.1007/s10735-023-10124-x. Epub 2023 May 9.

Administration of necrostatin-1 ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats

Min Feng  1 , Ruirui Zhang  2 , Mingming Zhang  3 , Ming Chen  1 , Le Ji  1 , Dapeng Duan  1 , Hui Qiang  4
Affiliations

Administration of necrostatin-1 ameliorates glucocorticoid-induced osteonecrosis of the femoral head in rats

Min Feng et al. J Mol Histol. 2023 Jun.

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.

Keywords: Glucocorticoids; Necroptosis; Necrostatin-1; Osteogenesis; Osteonecrosis of the femoral head.

PubMed Disclaimer

References

    1. Ansari N, Ho PW, Crimeen-Irwin B et al (2018) Autocrine and Paracrine Regulation of the murine skeleton by osteocyte-derived parathyroid hormone-related protein. J bone mineral research: official J Am Soc Bone Mineral Res 33(1):137–153. https://doi.org/10.1002/jbmr.3291 - DOI
    1. Bei J, Zhang X, Wu J et al (2018) Ginsenoside Rb1 does not halt osteoporotic bone loss in ovariectomized rats. PLoS ONE 13(9):e0202885. https://doi.org/10.1371/journal.pone.0202885 - DOI - PubMed - PMC
    1. Calder JD, Buttery L, Revell PA et al (2004) Apoptosis–a significant cause of bone cell death in osteonecrosis of the femoral head. J Bone Joint Surg Br 86(8):1209–1213. https://doi.org/10.1302/0301-620x.86b8.14834 - DOI - PubMed
    1. Chang C, Greenspan A, Gershwin ME (2020) The pathogenesis, diagnosis and clinical manifestations of steroid-induced osteonecrosis. J Autoimmun 110:102460. https://doi.org/10.1016/j.jaut.2020.102460 - DOI - PubMed
    1. Chotiyarnwong P, Mccloskey EV (2020) Pathogenesis of glucocorticoid-induced osteoporosis and options for treatment. Nat Rev Endocrinol 16(8):437–447. https://doi.org/10.1038/s41574-020-0341-0 - DOI - PubMed

MeSH terms

LinkOut - more resources