DGCR5 induces osteogenic differentiation by up-regulating Runx2 through miR-30d-5p

Biochem Biophys Res Commun. 2018 Oct 28;505(2):426-431. doi: 10.1016/j.bbrc.2018.09.033. Epub 2018 Sep 25.

Abstract

Background: Postmenopausal osteoporosis (PMOP) is a metabolic bone disease caused by unbalance between osteoblast bone formation and osteoclast bone resorption. In this study, the moderating effect of DGCR5 on osteogenic differentiation and its role in PMOP was assessed.

Methods: The expression levels of DGCR5, miR-30d-5p, and Runt-related transcription factor 2 (Runx2) mRNA and protein were determined by qRT-PCR and western blot, separately. The bone marrow human mesenchymal stem cells (hMSCs) were isolated from bone marrow of patients with PMOP or the healthy control. ALP activity and bone mineral density (BMD) were detected to reflect the osteogenic differentiation status. RIP and RNA pull-down assay were performed to explore the combination and interaction between DGCR5 and miR-30d-5p.

Results: Compared with the healthy control group (n = 20), DGCR5 was down-regulated in hMSCs from patients with PMOP (n = 20). Overexpression of DGCR5 induced osteogenic differentiation of hMSCs. DGCR5 up-regulated the expression of Runx2 through miR-30d-5p. DGCR5 up-regulated the expression of Runx2 through miR-30d-5p to induce osteogenic differentiation of hMSCs.

Conclusion: DGCR5 negatively regulates miR-30d-5p, and it up-regulates Runx2 through miR-30d-5p, thereby inducing osteogenic differentiation of hMSCs, which may help to delay PMOP development.

Keywords: DGCR5; Osteogenic differentiation; PMOP; Runx2; hMSCs; miR-30d-5p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Differentiation
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Humans
  • Mesenchymal Stem Cells / cytology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoblasts / cytology
  • Osteogenesis*
  • Osteoporosis, Postmenopausal / etiology
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • MIRN30b microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • RUNX2 protein, human
  • long noncoding RNA DGCR5, human