MiR-26b-3p regulates osteoblast differentiation via targeting estrogen receptor α

Genomics. 2019 Sep;111(5):1089-1096. doi: 10.1016/j.ygeno.2018.07.003. Epub 2018 Jul 6.

Abstract

Background: Understanding of the molecular mechanisms of miRNAs involved in osteoblast differentiation is important for the treatment of bone-related diseases.

Methods: MC3T3-E1 cells were induced to osteogenic differentiation by culturing with bone morphogenetic protein 2 (BMP2). After transfected with miR-26b-3p mimics or inhibitors, the osteogenic differentiation of MC3T3-E1 cells was detected by ALP and ARS staining. Cell viability was analyzed by MTT. The expressions of miR-26b-3p and osteogenic related markers and signaling were examined by qPCR and western blot. Direct binding of miR-26b-3p and ER-α were determined by dual luciferase assay.

Results: miR-26b-3p was significantly down-regulated during osteoblast differentiation. Overexpression of miR-26b-3p inhibited osteoblast differentiation, while inhibition of miR-26b-3p enhanced osteoblast differentiation. Further studies demonstrated miR-26b-3p inhibited the expression of estrogen receptor α (ER-α) by directly targeting to the CDS region of ER-α mRNA. Overexpression of ER-α rescued the suppression effects of miR-26b-3p on osteoblast differentiation, while knockdown of ER-α reversed the upregulation of osteoblast differentiation induced by knockdown of miR-26b-3p.

Conclusion: Our study demonstrates that miR-26b-3p suppresses osteoblast differentiation of MC3T3-E1 cells via directly targeting ER-α.

Keywords: Bone regeneration; Estrogen receptor α; Osteoblast differentiation; miR-26b-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation*
  • Estrogen Receptor alpha / genetics*
  • Estrogen Receptor alpha / metabolism
  • HEK293 Cells
  • Humans
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*

Substances

  • Estrogen Receptor alpha
  • MicroRNAs
  • Mirn26 microRNA, mouse