The cytokine osteoprotegerin(OPG), also designated osteoclastogenesis inhibitory factor (OCIF), is known to inhibit osteoclast formation. A secreted glycoprotein, OPG is a member of the TNF receptor family that increases bone density and volume. OPG is thought to inhibit osteoclastogenesis by disrupting the cell-to-cell signaling between osteoblastic stromal cells and osteoclast progenitors. OPG is known to bind to TRAIL, a death domain-containing protein, and to inhibit TRAIL apoptosis in Jurkat cells. OPG also binds to osteoclast differentiation factor (ODF), also known as TRANCE/RANKL, a membrane-bound protein belonging to the TNF ligand family. Both TNF(alpha) and TNF(beta) upregulate OPG expression, while the bone resorbing agent prostaglandin E2 downregulates OPG.