Osteoprotegerin: a novel secreted protein involved in the regulation of bone density

  • Cell. 1997 Apr 18;89(2):309-19. doi: 10.1016/s0092-8674(00)80209-3.
W S Simonet  1 ,  D L Lacey ,  C R Dunstan ,  M Kelley ,  M S Chang ,  R Lüthy ,  H Q Nguyen ,  S Wooden ,  L Bennett ,  T Boone ,  G Shimamoto ,  M DeRose ,  R Elliott ,  A Colombero ,  H L Tan ,  G Trail ,  J Sullivan ,  E Davy ,  N Bucay ,  L Renshaw-Gegg ,  T M Hughes ,  D Hill ,  W Pattison ,  P Campbell ,  S Sander ,  G Van ,  J Tarpley ,  P Derby ,  R Lee ,  W J Boyle
Affiliations
  • 1. Department of Molecular Genetics, Amgen Inc., Thousand Oaks, California 91320, USA.
PMID: 9108485 DOI: 10.1016/s0092-8674(00)80209-3
Abstract

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.

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