osteoprotegerin-deficient mice develop early onset osteoporosis and arterial calcification.
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.
Bucay
N
N
Department of Molecular Genetics, Amgen, Inc., Thousand Oaks, California 91320-1789, USA.
Sarosi
I
I
Dunstan
C R
CR
Morony
S
S
Tarpley
J
J
Capparelli
C
C
Scully
S
S
Tan
H L
HL
Xu
W
W
Lacey
D L
DL
Boyle
W J
WJ
Simonet
W S
WS
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
D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506031:Tnfrsf11b protein, mouse