miR-486-5p Attenuates Steroid-Induced Adipogenesis and Osteonecrosis of the Femoral Head Via TBX2/P21 Axis

Stem Cells. 2023 Jul 14;41(7):711-723. doi: 10.1093/stmcls/sxad038.

Abstract

Enhanced adipogenic differentiation of mesenchymal stem cells (MSCs) is considered as a major risk factor for steroid-induced osteonecrosis of the femoral head (SOFNH). The role of microRNAs during this process has sparked interest. miR-486-5p expression was down-regulated significantly in femoral head bone tissues of both SONFH patients and rat models. The purpose of this study was to reveal the role of miR-486-5p on MSCs adipogenesis and SONFH progression. The present study showed that miR-486-5p could significantly inhibit adipogenesis of 3T3-L1 cells by suppressing mitotic clonal expansion (MCE). And upregulated expression of P21, which was caused by miR-486-5p mediated TBX2 decrease, was responsible for inhibited MCE. Further, miR-486-5p was demonstrated to effectively inhibit steroid-induced fat formation in the femoral head and prevented SONFH progression in a rat model. Considering the potent effects of miR-486-5p on attenuating adipogenesis, it seems to be a promising target for the treatment of SONFH.

Keywords: P21; TBX2; adipogenesis; mesenchymal stem cells; miR-486-5p; mitotic clonal expansion; steroid-induced osteonecrosis of the femoral head.

MeSH terms

  • Adipogenesis / genetics
  • Animals
  • Cell Differentiation / genetics
  • Femur Head / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteonecrosis* / chemically induced
  • Osteonecrosis* / metabolism
  • Rats
  • Steroids / adverse effects

Substances

  • MicroRNAs
  • Steroids
  • MIRN486 microRNA, rat
  • MIRN486 microRNA, human