miR-125a-5p Regulates Osteogenic Differentiation of Human Adipose-Derived Mesenchymal Stem Cells under Oxidative Stress

Biomed Res Int. 2021 Jun 7:2021:6684709. doi: 10.1155/2021/6684709. eCollection 2021.

Abstract

Adipose-derived mesenchymal stem cells (ADSCs) are a well-recognized multilineage stem cell with vital clinical feasibility for tissue regeneration. Extensive evidence indicates that oxidative stress and microRNAs (miRNAs/miRs) play an important role in the osteoinduction of adipose-derived mesenchymal stem cells. In this study, we investigated the mechanism of miR-125a-5p in regulating the osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs) under oxidative stress. The expression of miR-125a-5p lessened gradually during the osteogenic differentiation of hADSCs. Relative to the negative group, the expression levels of runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteocalcin (OCN), and osterix in the miR-125a-5p group were marked lower than those in the miR-125a-5p inhibitor group. The levels of p16, p21, p53, miR-125a-5p, and ROS during osteoinduction of hADSCs were assessed in vitro under oxidative stress and were observed to be upregulated. Further experiments showed that oxidative stress and miR-125a-5p together suppressed the expression of VEGF during osteogenic differentiation of hADSCs and that the inhibition of miR-125a-5p reversed the effect of oxidative stress. In short, our study indicated that miR-125a-5p is induced under oxidative stress and inhibits the expression of VEGF, leading to the reduction of osteogenic differentiation of hADSCs. Our outcomes showed that miR-125a-5p could be a potential clinical target for bone repairing.

MeSH terms

  • Adipocytes / cytology*
  • Alkaline Phosphatase / metabolism
  • Bone Remodeling
  • Bone and Bones / metabolism
  • Cell Differentiation
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • MicroRNAs / metabolism*
  • Osteoblasts / metabolism
  • Osteocalcin / metabolism
  • Osteogenesis / physiology
  • Oxidative Stress*
  • Sp7 Transcription Factor / metabolism
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • BGLAP protein, human
  • Core Binding Factor Alpha 1 Subunit
  • MIRN125 microRNA, human
  • MicroRNAs
  • RUNX2 protein, human
  • Sp7 Transcription Factor
  • SP7 protein, human
  • Vascular Endothelial Growth Factor A
  • Osteocalcin
  • Alkaline Phosphatase