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, 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
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