MiR-19b-3p regulates osteogenic differentiation of PDGFRα+ muscle cells by specifically targeting PTEN

Cell Biol Int. 2019 May;43(5):565-573. doi: 10.1002/cbin.11133. Epub 2019 Apr 25.

Abstract

Heterotopic ossification (HO) is a common disturbing complication of intra-articular fractures. Its prevention and treatment are still difficult as its pathogenesis is unclear. It was reported that PDGFRα+ muscle cells in skeletal muscle may participate in the formation of HO; however, the specific mechanism is still unknown. This study investigated the function of miR-19b-3p in osteogenic differentiation of PDGFRα+ muscle cells. MiR-19b-3p was upregulated during PDGFRα+ muscle cell osteogenic differentiation. The exogenous expression of miR-19b-3p led to an increase in osteogenic marker gene transcription and translation during the osteogenic differentiation of PDGFRα+ muscle cells. Furthermore, both alkaline phosphatase and alizarin red staining increased in miR-19b-3p mimic transfected cells. Over-expression of miR-19b-3p led to the down-regulation of gene of phosphate and tension homology deleted on chromosome ten (PTEN). Additionally, the dual luciferase reporter assay demonstrated that PTEN was a direct target of miR-19b-3p. The increase of osteocalcin, osteopontin, and Runt-related transcription factor 2 protein levels induced by ectopic miR-19b-3p expression could be partially reversed by PTEN over-expression. In conclusion, our results suggested that miR-19b-3p may be a promising target in inhibiting PDGFRα+ muscle cell osteogenic differentiation and treatment of HO.

Keywords: PDGFRα+ muscle cells; PTEN; heterotopic ossification; miR-19b-3p; osteogenesis.

MeSH terms

  • Cell Differentiation / physiology
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Down-Regulation
  • Humans
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Ossification, Heterotopic / genetics
  • Ossification, Heterotopic / metabolism*
  • Ossification, Heterotopic / pathology
  • Osteocalcin / metabolism
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism*
  • Receptor, Platelet-Derived Growth Factor alpha / genetics
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • MIRN19 microRNA, human
  • MicroRNAs
  • Osteocalcin
  • Receptor, Platelet-Derived Growth Factor alpha
  • PTEN Phosphohydrolase
  • PTEN protein, human