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 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, 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 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
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.
Source: PubMed