OSTEOPROTEGERIN - A NOVEL SECRETED PROTEIN INVOLVED IN THE REGULATIONOF BONE-DENSITY

A novel secreted glycoprotein that regulates bone resorption has been identified. The protein, termed Osteoprotegerin (OPG), is a novel memb er 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 differentiat ion. These same effects are observed upon administration of recombinan t OPG into normal mice. In vitro, osteoclast differentiation from prec ursor cells is blocked in a dose-dependent manner by recombinant OPG. Furthermore, OPG blocks ovariectomy-associated bone loss in rats. Thes e 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.