Resveratrol prevents steroid‐induced osteonecrosis of the femoral head via miR‐146a modulation

Abstract

The purpose of this study was to investigate the possible use of resveratrol (Res) to reverse abnormal osteogenesis/osteoclastogenesis activity that occurs during femoral head osteonecrosis and to explore the detailed mechanisms. Application of Res to bone marrow–derived mesenchymal stem cells in vitro promoted survival, inhibited apoptosis, and downregulated expression of reactive oxygen species expression. Moreover, Res application was associated with elevated microRNA‐146a (miR‐146a) expression, osteogenic differentiation, and suppressed osteoclastic differentiation, which were markedly reversed by miR‐146a inhibitor. Histopathological observations and micro‐computed tomography scanning results indicated that the Res‐treated group had lower incidence of osteonecrosis and better bone microstructure than the untreated group. Res inhibited osteoclastogenesis through altering the levels of sirtuin1 (Sirt1), nuclear transcription factor‐κB (NF‐κB), and receptor activator of NF‐κB ligand (RANKL). Simultaneously, Res treatment improved bone formation and increased β‐catenin and runt‐related transcription factor 2 (Runt2) expression levels, while reducing forkhead box class O (FOXO) family protein levels. The results of our study suggest that Res prevents steroid‐induced osteonecrosis by upregulating miR‐146a, and thereby stabilizes osteogenesis/osteoclastogenesis homeostasis via Wnt/FOXO and Sirt1/NF‐κB pathways.

Bone marrow mesenchymal stem cells‐derived exosomes mediate nuclear receptor coactivator‐3 expression in osteoblasts by delivering miR‐532‐5p to influence osteonecrosis of the femoral head development

“…Protein levels are determined as previously described (Nan, Pei, et al, 2021). Cell and tissue samples were lysed in radio‐immunoprecipitation assay buffer and centrifuged.…”

Functional micro-RNA drugs acting as a fate manipulator in the regulation of osteoblastic death

“…Another debated one is miR-146a, which was reported to be engaged in both promoting and inhibiting osteoblastic apoptosis. 74,75 Cao et al demonstrated that the expression of caspase-3 and Bax could be inhibited by downregulation of miR-146a. Thus, making use of the competitive endogenous RNA (ce-RNA) mechanism of circRNA–Rtn4 to sponge miR-146a can significantly attenuate apoptosis in osteoblasts.…”

“…75 Differently, Nan et al reported that miR-146a could protect against steroid-induced osteonecrosis. 74 They showed that miR-146a down-regulated the ROS levels and protected bone trabecular structures via down-mediating the Wnt/FOXO signaling pathway.…”

Preclinical models for studying corticosteroid‐induced osteonecrosis of the femoral head

“…79,80 Nan et al investigated the effect of resveratrol on the abnormal bone formation and osteoclastogenic activity that occurs in the pathogenesis of steroid-induced femoral head necrosis. 65 Application of resveratrol to BMSCs in vitro inhibited apoptosis, promoted survival, and downregulated the expression of reactive oxygen species. In addition, resveratrol was associated with osteogenic differentiation and increased microRNA-146a expression, suggesting that resveratrol may prevent ONFH.…”

“…Resveratrol is a polyphenol compound found in various types of natural fruits and plants, has antioxidant properties 79,80 . Nan et al investigated the effect of resveratrol on the abnormal bone formation and osteoclastogenic activity that occurs in the pathogenesis of steroid‐induced femoral head necrosis 65 . Application of resveratrol to BMSCs in vitro inhibited apoptosis, promoted survival, and downregulated the expression of reactive oxygen species.…”