Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL.
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.
Emery
J G
JG
Department of Molecular Biology, King of Prussia, Pennsylvania 19406, USA.
McDonnell
P
P
Burke
M B
MB
Deen
K C
KC
Lyn
S
S
Silverman
C
C
Dul
E
E
Appelbaum
E R
ER
Eichman
C
C
DiPrinzio
R
R
Dodds
R A
RA
James
I E
IE
Rosenberg
M
M
Lee
J C
JC
Young
P R
PR
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*
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