title: osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
abstract: Osteoprotegerin (OPG) is a secreted protein that inhibits osteoclast formation. In this study the physiological role of OPG is investigated by generating OPG-deficient mice. Adolescent and adult OPG-/- mice exhibit a decrease in total bone density characterized by severe trabecular and cortical bone porosity, marked thinning of the parietal bones of the skull, and a high incidence of fractures. These findings demonstrate that OPG is a critical regulator of postnatal bone mass. Unexpectedly, OPG-deficient mice also exhibit medial calcification of the aorta and renal arteries, suggesting that regulation of OPG, its signaling pathway, or its ligand(s) may play a role in the long observed association between osteoporosis and vascular calcification.
authors.affiliation: Department of Molecular Genetics, Amgen, Inc., Thousand Oaks, California 91320-1789, USA.
authors.forename: N
authors.initials: N
authors.lastname: Bucay
authors.forename: I
authors.initials: I
authors.lastname: Sarosi
authors.forename: C R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: S
authors.initials: S
authors.lastname: Morony
authors.forename: J
authors.initials: J
authors.lastname: Tarpley
authors.forename: C
authors.initials: C
authors.lastname: Capparelli
authors.forename: S
authors.initials: S
authors.lastname: Scully
authors.forename: H L
authors.initials: HL
authors.lastname: Tan
authors.forename: W
authors.initials: W
authors.lastname: Xu
authors.forename: D L
authors.initials: DL
authors.lastname: Lacey
authors.forename: W J
authors.initials: WJ
authors.lastname: Boyle
authors.forename: W S
authors.initials: WS
authors.lastname: Simonet
mesh_terms: D000818:Animals; D001158:Arteries / Q000473:pathology; D015519:Bone Density / Q000235:genetics / Q000502:physiology; D002114:Calcinosis / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D018390:Gene Targeting; D006023:Glycoproteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010024:Osteoporosis / Q000209:etiology* / Q000473:pathology; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D014652:Vascular Diseases / Q000209:etiology* / Q000473:pathology
chemical_list: D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse