MiR-217 promotes cell proliferation and osteogenic differentiation of BMSCs by targeting DKK1 in steroid-associated osteonecrosis

Biomed Pharmacother. 2019 Jan:109:1112-1119. doi: 10.1016/j.biopha.2018.10.166. Epub 2018 Nov 6.

Abstract

MicroRNAs (miRNAs) have recently been recognized to play an important role in bone-associated diseases. This study aims to explore the expression profile and biological function of miR-217, which is known to be related to tumor cell proliferation and migration, to the proliferation and osteogenic differentiation of MSCs from the patients with steroid-associated osteonecrosis (ONFH). Bone marrow was obtained from the proximal femur of 10 patients with ONFH and 10 patients with femoral neck fractures. Bone marrow-derived mesenchymal stem cells (MSCs) were isolated and cultured. The expression profile, biological function of miR-217 and the interaction between miR-217 and DKK1 were assayed using cell viability measurement, western blot, Real-time PCR, luciferase reporter assay, Alizarin Red S (ARS) staining. We noted that the expression level of miR-217 was significantly decreased in the ONFH samples compared to the control samples (P < 0.0001). By targeting DKK1, miR-217 promoted nuclear translocation of β-catenin, increased expression of RUNX2, COL1A1 and obviously promoted the proliferation and differentiation of MSCs. Restoring the expression of DKK1 in the MSCs partially reversed the role of miR-217. These findings suggest that miR-217 promotes cell proliferation and osteogenic differentiation by inhibiting DKK1 during the development of steroid-associated osteonecrosis.

Keywords: DKK1; Mesenchymal stem cells; MiR-217; Osteonecrosis.

MeSH terms

  • Aged
  • Bone Marrow / physiology*
  • Cell Differentiation / genetics*
  • Cell Line
  • Cell Proliferation / genetics*
  • Cell Survival / genetics
  • Collagen Type I / genetics
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Male
  • Mesenchymal Stem Cells / physiology*
  • MicroRNAs / genetics*
  • Middle Aged
  • Osteogenesis / genetics*
  • Steroids / metabolism
  • beta Catenin / genetics

Substances

  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Core Binding Factor Alpha 1 Subunit
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN217 microRNA, human
  • MicroRNAs
  • Steroids
  • beta Catenin