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

W. S. Simonet, 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. Trall, J. Sullivan, E. Davy, N. Bucay, L. Renshaw-GeggT. M. Hughes, D. Hill, W. Pattison, P. Campbell, S. Sander, G. Van, J. Tarpley, P. Derby, R. Lee, W. J. Boyle

Research output: Contribution to journalArticlepeer-review

4310 Citations (Scopus)


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 non-lethal 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.

Original languageEnglish
Pages (from-to)309-319
Number of pages11
Issue number2
Publication statusPublished - 1997 Apr 18

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)


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