Cellular activity and signaling induced by osteoprotegerin in osteoclasts: involvement of receptor activator of nuclear factor kappaB ligand and MAPK

Biochim Biophys Acta. 2004 Feb 2;1644(1):1-7. doi: 10.1016/j.bbamcr.2003.10.005.

Abstract

Osteoprotegerin (OPG) is a decoy receptor for receptor activator of nuclear factor kappaB ligand (RANKL), an inducer of osteoclastogenesis via its receptor RANK. We recently demonstrated that OPG also exerts a direct effect in osteoclasts by regulating protease expression. Herein, we showed that OPG-induced pro-matrix metalloproteinase-9 activity was abolished by ras/MAPK inhibitors in purified osteoclasts. OPG induced the phosphorylation of p38 and ERK1/2 in RAW264.7 cells. Only p38 activation was totally abolished by a blocking anti-RANKL antibody or an excess of RANKL. Surface plasmon resonance experiments revealed that RANK, RANKL and OPG are able to form a tertiary complex. These results suggested a potential formation of a tertiary complex RANK-RANKL-OPG on osteoclasts. Thus, OPG is not only a soluble decoy receptor for RANKL but must be also considered as a direct effector of osteoclast functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / antagonists & inhibitors
  • Carrier Proteins / pharmacology
  • Cell Line
  • Cells, Cultured
  • Enzyme Activation
  • Glycoproteins / antagonists & inhibitors
  • Glycoproteins / pharmacology
  • Glycoproteins / physiology*
  • Ligands
  • Matrix Metalloproteinase 9 / biosynthesis
  • Matrix Metalloproteinase Inhibitors
  • Membrane Glycoproteins / antagonists & inhibitors
  • Membrane Glycoproteins / pharmacology
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Models, Molecular
  • Osteoclasts / drug effects
  • Osteoclasts / enzymology
  • Osteoclasts / metabolism*
  • Osteoprotegerin
  • Phosphorylation
  • RANK Ligand
  • Rabbits
  • Receptors, Cytoplasmic and Nuclear / antagonists & inhibitors
  • Receptors, Cytoplasmic and Nuclear / physiology*
  • Receptors, Tumor Necrosis Factor
  • Signal Transduction / physiology
  • Surface Plasmon Resonance
  • Transfection
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Carrier Proteins
  • Glycoproteins
  • Ligands
  • Matrix Metalloproteinase Inhibitors
  • Membrane Glycoproteins
  • Osteoprotegerin
  • RANK Ligand
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Tumor Necrosis Factor
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 9