Regulation of matrix metalloproteinase-9 protein expression by 1α, 25-(OH)₂D₃ during osteoclast differentiation

J Vet Sci. 2014;15(1):133-40. doi: 10.4142/jvs.2014.15.1.133. Epub 2013 Oct 18.

Abstract

To investigate 1α,25-(OH)₂D₃ regulation of matrix metalloproteinase-9 (MMP-9) protein expression during osteoclast formation and differentiation, receptor activator of nuclear factor kB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) were administered to induce the differentiation of RAW264.7 cells into osteoclasts. The cells were incubated with different concentrations of 1α,25-(OH)₂D₃ during culturing, and cell proliferation was measured using the methylthiazol tetrazolium method. Osteoclast formation was confirmed using tartrate-resistant acid phosphatase (TRAP) staining and assessing bone lacunar resorption. MMP-9 protein expression levels were measured with Western blotting. We showed that 1α,25-(OH)₂D₃ inhibited RAW264.7 cell proliferation induced by RANKL and M-CSF, increased the numbers of TRAP-positive osteoclasts and their nuclei, enhanced osteoclast bone resorption, and promoted MMP-9 protein expression in a concentration-dependent manner. These findings indicate that 1α,25-(OH)₂D₃ administered at a physiological relevant concentration promoted osteoclast formation and could regulate osteoclast bone metabolism by increasing MMP-9 protein expression during osteoclast differentiation.

Keywords: 1α,25-(OH)₂D₃; MMP-9; TRAP; bone lacunar resorption; osteoclast.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Animals
  • Blotting, Western
  • Calcitriol / pharmacology*
  • Calcium Channel Agonists / pharmacology
  • Cell Differentiation*
  • Cell Line
  • Cell Proliferation
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Isoenzymes / metabolism
  • Matrix Metalloproteinase 9 / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Mice
  • Osteoclasts / cytology*
  • Osteoclasts / enzymology*
  • Tartrate-Resistant Acid Phosphatase
  • Tetrazolium Salts
  • Thiazoles

Substances

  • Calcium Channel Agonists
  • Isoenzymes
  • Tetrazolium Salts
  • Thiazoles
  • Acid Phosphatase
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase
  • Matrix Metalloproteinase 9
  • thiazolyl blue
  • Calcitriol