title: Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation.
abstract: The ligand for osteoprotegerin has been identified, and it is a TNF-related cytokine that replaces the requirement for stromal cells, vitamin D3, and glucocorticoids in the coculture model of in vitro osteoclastogenesis. OPG ligand (OPGL) binds to a unique hematopoeitic progenitor cell that is committed to the osteoclast lineage and stimulates the rapid induction of genes that typify osteoclast development. OPGL directly activates isolated mature osteoclasts in vitro, and short-term administration into normal adult mice results in osteoclast activation associated with systemic hypercalcemia. These data suggest that OPGL is an osteoclast differentiation and activation factor. The effects of OPGL are blocked in vitro and in vivo by OPG, suggesting that OPGL and OPG are key extracellular regulators of osteoclast development.
authors.affiliation: Department of Pathology, Amgen, Inc., Thousand Oaks, California 91320-1789, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Lacey
authors.forename: E
authors.initials: E
authors.lastname: Timms
authors.forename: H L
authors.initials: HL
authors.lastname: Tan
authors.forename: M J
authors.initials: MJ
authors.lastname: Kelley
authors.forename: C R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: T
authors.initials: T
authors.lastname: Burgess
authors.forename: R
authors.initials: R
authors.lastname: Elliott
authors.forename: A
authors.initials: A
authors.lastname: Colombero
authors.forename: G
authors.initials: G
authors.lastname: Elliott
authors.forename: S
authors.initials: S
authors.lastname: Scully
authors.forename: H
authors.initials: H
authors.lastname: Hsu
authors.forename: J
authors.initials: J
authors.lastname: Sullivan
authors.forename: N
authors.initials: N
authors.lastname: Hawkins
authors.forename: E
authors.initials: E
authors.lastname: Davy
authors.forename: C
authors.initials: C
authors.lastname: Capparelli
authors.forename: A
authors.initials: A
authors.lastname: Eli
authors.forename: Y X
authors.initials: YX
authors.lastname: Qian
authors.forename: S
authors.initials: S
authors.lastname: Kaufman
authors.forename: I
authors.initials: I
authors.lastname: Sarosi
authors.forename: V
authors.initials: V
authors.lastname: Shalhoub
authors.forename: G
authors.initials: G
authors.lastname: Senaldi
authors.forename: J
authors.initials: J
authors.lastname: Guo
authors.forename: J
authors.initials: J
authors.lastname: Delaney
authors.forename: W J
authors.initials: WJ
authors.lastname: Boyle
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001862:Bone Resorption; D002352:Carrier Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000378:metabolism*; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D006934:Hypercalcemia; D008024:Ligands; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism*; D053244:Osteoprotegerin; D011485:Protein Binding; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins
chemical_list: D002352:Carrier Proteins; D016207:Cytokines; D006023:Glycoproteins; D008024:Ligands; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C505687:Tnfrsf11a protein, mouse; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat; C505689:Tnfsf11 protein, mouse; D016173:Macrophage Colony-Stimulating Factor