MicroRNA-29b Enhances Osteoclast Survival by Targeting BCL-2-Modifying Factor after Lipopolysaccharide Stimulation

Oxid Med Cell Longev. 2019 Apr 10:2019:6018180. doi: 10.1155/2019/6018180. eCollection 2019.

Abstract

Recent findings suggest that microRNAs (miRs) play a critical role in osteoclastogenesis, which regulates bone loss. We hypothesized that inflammation induces miR-29b, which increases the survival rate in osteoclasts (OCs), leading to bone loss. The expression level of miR-29b increased in OC stimulated by lipopolysaccharide (LPS) in an in vitro system which correlated with its increase in tibiae from mice that received LPS injections compared with those that received vehicle treatment. An miR-29b mimic increased OC survival rate without any change in OC differentiation, and furthermore, the inhibition of endogenous miR-29b induced by LPS decreased OC survival rate. Increased OC survival rate after overexpression of miR-29b was associated with antiapoptotic activity, as shown by staining annexin V-positive cells. We found that a target gene of miR-29b is BCL-2-modifying factor (Bmf), which acts as a proapoptotic factor, and that miR-29b binds to the 3'-UTR of Bmf. Our data demonstrate that LPS-induced miR-29b increases the number of OC by enhancing OC survival through decreased BMF.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Animals, Newborn
  • Base Sequence
  • Cell Count
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • Lipopolysaccharides / pharmacology*
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism*
  • Up-Regulation / drug effects

Substances

  • 3' Untranslated Regions
  • Adaptor Proteins, Signal Transducing
  • Bmf protein, mouse
  • Lipopolysaccharides
  • MIRN29 microRNA, mouse
  • MicroRNAs