MiR-920 promotes osteogenic differentiation of human bone mesenchymal stem cells by targeting HOXA7

J Orthop Surg Res. 2020 Jul 10;15(1):254. doi: 10.1186/s13018-020-01775-7.

Abstract

Background: To explore the effect of miR-920 on osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs) and the possible mechanism.

Methods: Osteoporosis (OP) and healthy control bone tissues were collected, and the relative expression of miR-920 and HOXA7 was measured. hBMSCs were isolated and cultured in vitro. Alkaline phosphatase activity and miR-920 and HOXA7 relative expression were measured during osteogenic differentiation of hBMSCs. Then, bioinformatic analysis was performed to assess the potential mechanism of miR-920. MiR-920 mimic and inhibitor were introduced into hBMSCs by lipofection transfection and were used to investigate the effect of miR-920 on the osteogenic differentiation of hBMSCs. A dual luciferase reporter assay was used to identify whether the 3'UTR of HOXA7 mRNA was a direct target of miR-920. Western blotting was performed to assess whether miR-920 affected the MAPK signaling pathway.

Results: We found that miR-920 was downregulated in OP patients compared with controls, while HOXA7 was upregulated, and miR-920 had a negative correlation with HOXA7 (r = - 0.859, P = 0.001). Moreover, miR-920 was increased during osteogenic differentiation of hBMSCs, while HOXA7 had the opposite tendency. Bioinformatic analysis revealed that there were a total of 207 target genes, and MAPK was a potential targeted signaling pathway. MiR-920 mimic significantly increased ALP activity, calcium deposition, osteoblastic protein expression (ALP and OSX), and p-p38 and p-JNK protein levels.

Conclusion: Overall, miR-920 promotes osteogenic differentiation of hBMSCs by targeting HOXA7 through the MAPK signaling pathway.

Keywords: HOXA7; Human bone mesenchymal stem cells; MiR-920; Osteogenic differentiation.

MeSH terms

  • Bone and Bones / cytology*
  • Cell Differentiation / genetics*
  • Cells, Cultured
  • Gene Expression / drug effects
  • Gene Expression / genetics
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / genetics
  • Homeodomain Proteins / genetics*
  • Homeodomain Proteins / metabolism*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • Mesenchymal Stem Cells / physiology*
  • MicroRNAs / pharmacology*
  • MicroRNAs / physiology*
  • Osteogenesis / genetics*

Substances

  • HOXA7 protein, human
  • Homeodomain Proteins
  • MIRN920 microRNA, human
  • MicroRNAs