Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel member of the TNF receptor superfamily. In vivo, hepatic expression of OPG in transgenic mice results in a profound yet nonlethal osteopetrosis, coincident with a decrease in later stages of osteoclast differentiation. These same effects are observed upon administration of recombinant OPG into normal mice. In vitro, osteoclast differentiation from precursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rats. These data show that OPG can act as a soluble factor in the regulation of bone mass and imply a utility for OPG in the treatment of osteoporosis associated with increased osteoclast activity.
Simonet
W S
WS
Department of Molecular Genetics, Amgen Inc., Thousand Oaks, California 91320, USA.
Lacey
D L
DL
Dunstan
C R
CR
Kelley
M
M
Chang
M S
MS
Lüthy
R
R
Nguyen
H Q
HQ
Wooden
S
S
Bennett
L
L
Boone
T
T
Shimamoto
G
G
DeRose
M
M
Elliott
R
R
Colombero
A
A
Tan
H L
HL
Trail
G
G
Sullivan
J
J
Davy
E
E
Bucay
N
N
Renshaw-Gegg
L
L
Hughes
T M
TM
Hill
D
D
Pattison
W
W
Campbell
P
P
Sander
S
S
Van
G
G
Tarpley
J
J
Derby
P
P
Lee
R
R
Boyle
W J
WJ
D000595:Amino Acid Sequence; D000818:Animals; D015519:Bone Density / Q000502:physiology*; D001862:Bone Resorption; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D010022:Osteopetrosis / Q000235:genetics* / Q000378:metabolism; D053244:Osteoprotegerin; D010052:Ovariectomy; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; D017386:Sequence Homology, Amino Acid
D006023:Glycoproteins; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; D011993:Recombinant Fusion Proteins; C506030:TNFRSF11B protein, human; C506031:Tnfrsf11b protein, mouse; C506032:Tnfrsf11b protein, rat