Bone morphogenesis and remodeling involve the formation of bone from osteoblasts and the resorption of bone by osteoclasts. 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 TNFα and TNFβ upregulate OPG expression, while the bone resorbing agent prostaglandin E2 downregulates OPG.