Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL

J Biol Chem. 1998 Jun 5;273(23):14363-7. doi: 10.1074/jbc.273.23.14363.

Abstract

TRAIL is a tumor necrosis factor-related ligand that induces apoptosis upon binding to its death domain-containing receptors, DR4 and DR5. Two additional TRAIL receptors, TRID/DcR1 and DcR2, lack functional death domains and function as decoy receptors for TRAIL. We have identified a fifth TRAIL receptor, namely osteoprotegerin (OPG), a secreted tumor necrosis factor receptor homologue that inhibits osteoclastogenesis and increases bone density in vivo. OPG-Fc binds TRAIL with an affinity of 3.0 nM, which is slightly weaker than the interaction of TRID-Fc or DR5-Fc with TRAIL. OPG inhibits TRAIL-induced apoptosis of Jurkat cells. Conversely, TRAIL blocks the anti-osteoclastogenic activity of OPG. These data suggest potential cross-regulatory mechanisms by OPG and TRAIL.

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Binding, Competitive
  • GPI-Linked Proteins
  • Glycoproteins / physiology*
  • Humans
  • Immunoglobulin Fc Fragments / genetics
  • Immunohistochemistry
  • Jurkat Cells
  • Ligands
  • Membrane Glycoproteins / physiology*
  • Mice
  • Microscopy, Fluorescence
  • Oligopeptides
  • Osteoclasts / cytology
  • Osteoprotegerin
  • Peptides / immunology
  • Protein Binding / physiology
  • Receptors, Cytoplasmic and Nuclear*
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor / classification
  • Receptors, Tumor Necrosis Factor / metabolism
  • Receptors, Tumor Necrosis Factor / physiology*
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Receptors, Tumor Necrosis Factor, Member 25
  • Recombinant Fusion Proteins / metabolism
  • TNF-Related Apoptosis-Inducing Ligand
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha / physiology*

Substances

  • Apoptosis Regulatory Proteins
  • GPI-Linked Proteins
  • Glycoproteins
  • Immunoglobulin Fc Fragments
  • Ligands
  • Membrane Glycoproteins
  • Oligopeptides
  • Osteoprotegerin
  • Peptides
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, TNF-Related Apoptosis-Inducing Ligand
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Member 10c
  • Receptors, Tumor Necrosis Factor, Member 25
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFRSF10B protein, human
  • TNFRSF10C protein, human
  • TNFRSF11B protein, human
  • TNFRSF25 protein, human
  • TNFSF10 protein, human
  • Tnfrsf10b protein, mouse
  • Tnfrsf11b protein, mouse
  • Tnfrsf25 protein, mouse
  • Tnfsf10 protein, mouse
  • Tumor Necrosis Factor Decoy Receptors
  • Tumor Necrosis Factor-alpha
  • FLAG peptide