miR-29a modulates tumor necrosis factor-α-induced osteogenic inhibition by targeting Wnt antagonists

Dev Growth Differ. 2015 Apr;57(3):264-73. doi: 10.1111/dgd.12207. Epub 2015 Apr 2.

Abstract

We previously found that miR-29a was significantly downregulated in Ankylosing spondylitis (AS) patients, a chronic inflammatory disease associated with bone metabolic disorder, however, the underlying mechanism remains unclear. In this study, we demonstrated that miR-29a regulates tumor necrosis factor-α (TNF-α) mediated bone loss mainly by targeting DKK1 and GSK3β, thus activating the Wnt/β-catenin pathway. Our findings may provide new insight into the pathogenesis of the bone metabolism disorder in inflammation environment and provide promising therapeutic target.

Keywords: TNF-α; Wnt antagonists; miR-29a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthraquinones
  • Blotting, Western
  • Bone Resorption / metabolism*
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Luciferases
  • MicroRNAs / metabolism*
  • Oligonucleotides / genetics
  • Real-Time Polymerase Chain Reaction
  • Spondylitis, Ankylosing / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism*
  • Wnt Signaling Pathway / physiology*

Substances

  • Anthraquinones
  • DKK1 protein, human
  • Intercellular Signaling Peptides and Proteins
  • MIRN29a microRNA, human
  • MicroRNAs
  • Oligonucleotides
  • Tumor Necrosis Factor-alpha
  • alizarin
  • Luciferases
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Glycogen Synthase Kinase 3