MiR-126-5p regulates osteoclast differentiation and bone resorption in giant cell tumor through inhibition of MMP-13

Biochem Biophys Res Commun. 2014 Jan 17;443(3):944-9. doi: 10.1016/j.bbrc.2013.12.075. Epub 2013 Dec 19.

Abstract

Giant cell tumor (GCT) of bone is an aggressive skeletal tumor characterized by localized bone resorption. Matrix metalloproteinase-13 (MMP-13) is the principal proteinase expressed by the stromal cells of GCT (GCTSCs) and also considered to play a crucial role in formation of the osteolytic lesion in GCT. However, the exact mechanism of the regulation of MMP-13 expression in GCTSCs was unknown. In this study, we identified miR-126-5p was significantly downregulated in GCTSCs and affect osteoclast (OC) differentiation and bone resorption by repressing MMP-13 expression at the post-transcriptional level. Thus, our studies show that miR-126-5p plays an important physiological role in multinucleated giant cell formation and osteolytic lesion in GCT.

Keywords: GCT; MMP-13; MiR-126-5p; Osteoclast differentiation; Osteolysis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Base Sequence
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / genetics
  • Bone Neoplasms / metabolism
  • Bone Neoplasms / pathology
  • Bone Resorption / enzymology
  • Bone Resorption / genetics
  • Bone Resorption / pathology*
  • Cell Differentiation / genetics*
  • Cell Line
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic
  • Genetic Engineering
  • Giant Cell Tumor of Bone / enzymology*
  • Giant Cell Tumor of Bone / genetics
  • Giant Cell Tumor of Bone / metabolism
  • Giant Cell Tumor of Bone / pathology*
  • Giant Cells / metabolism
  • Giant Cells / pathology
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Molecular Sequence Data
  • Osteoclasts / enzymology
  • Osteoclasts / pathology*
  • Protein Binding / genetics
  • Stromal Cells / enzymology
  • Stromal Cells / pathology

Substances

  • 3' Untranslated Regions
  • MIRN126 microRNA, human
  • MicroRNAs
  • MMP13 protein, human
  • Matrix Metalloproteinase 13