MicroRNA-467g inhibits new bone regeneration by targeting Ihh/Runx-2 signaling

Int J Biochem Cell Biol. 2017 Apr:85:35-43. doi: 10.1016/j.biocel.2017.01.018. Epub 2017 Feb 2.

Abstract

MicroRNAs are important post transcriptional regulators of gene expression and play critical role in osteoblast differentiation. In this study we report miR-467g, an uncharacterized novel miRNA, in regulation of osteoblast functions. Over-expression of miR-467g inhibited osteoblast differentiation. Target prediction analysis tools and experimental validation by luciferase 3' UTR reporter assay identified Runx-2 as a direct target of miR-467g. Over expression of miR-467g in osteoblasts down regulated Runx-2 and Ihh signaling components. Furthermore, silencing of miR-467g was done to see its role in Ihh and Runx-2 mediated bone healing and regeneration in a drill hole injury model in BALB/c mice. Silencing of miR-467g led to significant increase in new bone regeneration and Ihh and Runx-2 localization at injury site in a day dependent manner. In conclusion, miR-467g negatively regulates osteogenesis by targeting Ihh/Runx-2 signaling. We, thus, propose that therapeutic approaches targeting miR-467g could be useful in enhancing the new bone formation.

Keywords: Hedgehog signaling; MicroRNA; Osteoblast differentiation; Runx-2; bone regeneration; osteogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Regeneration / genetics*
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / genetics*
  • Core Binding Factor Alpha 1 Subunit / metabolism
  • Female
  • Gene Expression
  • Hedgehog Proteins / genetics*
  • Hedgehog Proteins / metabolism
  • Immunohistochemistry
  • Mice
  • MicroRNAs / genetics*
  • Osteoblasts / cytology
  • Signal Transduction / genetics*

Substances

  • Core Binding Factor Alpha 1 Subunit
  • Hedgehog Proteins
  • MicroRNAs
  • ihh protein, mouse