MiR-203 is involved in osteoporosis by regulating DKK1 and inhibiting osteogenic differentiation of MSCs

Eur Rev Med Pharmacol Sci. 2018 Aug;22(16):5098-5105. doi: 10.26355/eurrev_201808_15703.

Abstract

Objective: To investigate whether miR-203 is involved in the osteogenic differentiation of rat mesenchymal stem cells (MSCs) by regulating DDK1, thus participating in the pathogenesis of osteoporosis.

Patients and methods: miR-203 expression in serum samples of 60 osteoporosis patients and 60 normal subjects was detected using Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) assay. MSCs were isolated from bone marrow of rats and then identified. Subsequently, the effects of miR-203 and DKK1 on osteogenic differentiation were estimated by alkaline phosphatase (ALP) activity, alizarin red staining, ALP staining, respectively. Expression levels of osteogenic-specific genes were detected by Western blot. Rescue experiments were conducted to confirm whether miR-203 could promote osteogenic differentiation of MSCs by inhibiting DKK1.

Results: Serum level of miR-203 in osteoporosis patients was significantly lower than that of the normal subjects. Overexpressed miR-203 in MSCs enhanced ALP activity, expression of osteogenic marker genes and the number of calcified cells. Additionally, miR-203 could bind to DKK1. The regulatory effect of miR-203 on osteogenic differentiation in MSCs was reversed by DKK1.

Conclusions: MiR-203 promotes the differentiation of rat MSCs into osteoblast-like cells, which may be associated with the regulation of DKK1 expression.

MeSH terms

  • Animals
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / biosynthesis*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Osteoblasts / metabolism
  • Osteogenesis / physiology*
  • Osteoporosis / genetics
  • Osteoporosis / metabolism*
  • Osteoporosis / pathology
  • Rats

Substances

  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN203 microRNA, human
  • MIRN203 microRNA, rat
  • MicroRNAs