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

Autor: Nan K; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Pei JP; Department of Orthopaedics, Wuhan General Hospital of Guangzhou Command, Wuhan, People's Republic of China., Fan LH; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Zhang YK; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Zhang X; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Liu K; Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China., Shi ZB; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Dang XQ; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China., Wang KZ; Department of Orthopaedics, the Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi, People's Republic of China.
Jazyk: angličtina
Zdroj: Annals of the New York Academy of Sciences [Ann N Y Acad Sci] 2021 Nov; Vol. 1503 (1), pp. 23-37. Date of Electronic Publication: 2021 Jan 17.
DOI: 10.1111/nyas.14555
Abstrakt: 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.
(© 2021 New York Academy of Sciences.)
Databáze: MEDLINE
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