miR-542-3p prevents ovariectomy-induced osteoporosis in rats via targeting SFRP1

J Cell Physiol. 2018 Sep;233(9):6798-6806. doi: 10.1002/jcp.26430. Epub 2018 Apr 16.

Abstract

Secreted frizzled-related protein-1 (SFRP1) is a negative regulatory molecule of the WNT signaling pathway and serves as a therapeutic target for bone formation in osteoporosis. In this study, we first established an ovariectomized (OVX) rat model to simulate postmenopausal osteoporosis and found significant changes in miR-542-3p and sFRP1 expression by RNA sequencing and qRT-PCR. In addition, there was a significant negative correlation between miR-542-3p and sFRP1 mRNA levels in postmenopausal women with osteoporosis. We found that miR-542-3p inhibited the expression of sFRP1 mRNA by luciferase reporter assay. When the miR-542-3p binding site in sFRP1 3'UTR was deleted, it did not affect its expression. Western blot results showed that miR-542-3p inhibited the expression of SFRP1 protein. The expression of SFRP1 was significantly increased in osteoblast-induced mesenchymal stem cells (MSC), whereas the expression of miR-542-3p was significantly decreased. And miR-542-3p transfected MSCs showed a significant increase in osteoblast-specific marker expression, indicating that miR-542-3p is necessary for MSC differentiation. Inhibition of miR-542-3p reduced bone formation, confirmed miR-542-3p play a role in bone formation in vivo. In general, these data suggest that miR-542-3p play an important role in bone formation via inhibiting SFRP1 expression and inducing osteoblast differentiation.

Keywords: SFRP1; differentiation; miRNA; osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites / physiology
  • Cell Differentiation / physiology
  • Cell Line
  • Female
  • HEK293 Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Membrane Proteins / metabolism*
  • Mesenchymal Stem Cells / metabolism
  • MicroRNAs / metabolism*
  • Osteoblasts / metabolism
  • Osteoporosis / metabolism*
  • Ovariectomy / methods
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / physiology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Membrane Proteins
  • MicroRNAs
  • RNA, Messenger
  • Sfrp1 protein, rat