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