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Cell. 1997 Apr 18;89(2):159-61.
Osteoprotegerin: a novel secreted protein involved in the regulation of bone density.
Simonet WS,
Lacey DL,
Dunstan CR,
Kelley M,
Chang MS,
Lüthy R,
Nguyen HQ,
Wooden S,
Bennett L,
Boone T,
Shimamoto G,
DeRose M,
Elliott R,
Colombero A,
Tan HL,
Trail G,
Sullivan J,
Davy E,
Bucay N,
Renshaw-Gegg L,
Hughes TM,
Hill D,
Pattison W,
Campbell P,
Sander S,
Van G,
Tarpley J,
Derby P,
Lee R,
Boyle WJ.
Department of Molecular Genetics, Amgen Inc., Thousand Oaks, California 91320, USA.
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.
PMID: 9108485 [PubMed - indexed for MEDLINE]