title: Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.
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.
authors.affiliation: Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Emery
authors.forename: P
authors.initials: P
authors.lastname: McDonnell
authors.forename: M B
authors.initials: MB
authors.lastname: Burke
authors.forename: K C
authors.initials: KC
authors.lastname: Deen
authors.forename: S
authors.initials: S
authors.lastname: Lyn
authors.forename: C
authors.initials: C
authors.lastname: Silverman
authors.forename: E
authors.initials: E
authors.lastname: Dul
authors.forename: E R
authors.initials: ER
authors.lastname: Appelbaum
authors.forename: C
authors.initials: C
authors.lastname: Eichman
authors.forename: R
authors.initials: R
authors.lastname: DiPrinzio
authors.forename: R A
authors.initials: RA
authors.lastname: Dodds
authors.forename: I E
authors.initials: IE
authors.lastname: James
authors.forename: M
authors.initials: M
authors.lastname: Rosenberg
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.forename: P R
authors.initials: PR
authors.lastname: Young
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins; D001667:Binding, Competitive; D058851:GPI-Linked Proteins; D006023:Glycoproteins / Q000502:physiology*; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics; D007150:Immunohistochemistry; D019169:Jurkat Cells; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D009842:Oligopeptides; D010010:Osteoclasts / Q000166:cytology; D053244:Osteoprotegerin; D010455:Peptides / Q000276:immunology; D011485:Protein Binding / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000145:classification / Q000378:metabolism / Q000502:physiology*; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053219:Receptors, Tumor Necrosis Factor, Member 25; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D053221:TNF-Related Apoptosis-Inducing Ligand; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D007141:Immunoglobulin Fc Fragments; D008024:Ligands; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D053244:Osteoprotegerin; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053219:Receptors, Tumor Necrosis Factor, Member 25; D011993:Recombinant Fusion Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C108661:TNFRSF10C protein, human; C506030:TNFRSF11B protein, human; C506033:TNFRSF25 protein, human; C505653:TNFSF10 protein, human; C505640:Tnfrsf10b protein, mouse; C506031:Tnfrsf11b protein, mouse; C506034:Tnfrsf25 protein, mouse; C505654:Tnfsf10 protein, mouse; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; C085706:FLAG peptide