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

Simonet, W. S.; Lacey, D. L.; Dunstan, C. R.; Kelley, M.; Chang, M.-S.; Lüthy, R.; Nguyen, H. Q.; Wooden, S.; Bennett, L.; Boone, T.; Shimamoto, G.; DeRose, M.; Elliott, R.; Colombero, A.; Tan, H.-L.; Trail, G.; Sullivan, J.; Davy, E.; Bucay, N.; Renshaw-Gegg, L.; Hughes, T. M.; Hill, D.; Pattison, W.; Campbell, P.; Sander, S.; Van, G.; Tarpley, J.; Derby, P.; Lee, R.; Boyle, W. J.

Affiliations

¹Department of Molecular Genetics, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

²Department of Pathology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

³Department of Protein Chemistry, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

⁴Department of Computational Biology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

⁵Department of Mammalian Cell Molecular Biology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

⁶Department of Immunology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

⁷Department of Process Science, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

⁸Department of Cell Biology, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

⁹Department of Bacterial Expression, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

¹⁰Department of Protein Structure, Amgen Inc., 1840 DeHavilland Drive, Thousand Oaks, California 91320

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.

Links

DOI: 10.1016/S0092-8674(00)80209-3

PubMed: 9108485

WoS: A1997WU88800017

History

Received: 1997-02-13

Revised: 1997-04-18

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