[Osteoclastogenesis inhibitory factor (OCIF)/OPG].

A novel cytokine termed osteoclastogenesis inhibitory factor (OCIF) was purified to homogeneity from conditioned medium of human embryonic lung fibroblasts. OCIF is a heparin-binding basic glycoprotein with Mr of 60 kDa for a monomer and 120 kDa for a homodimer. OCIF specifically inhibits osteoclastogenesis in vitro and increases bone mineral density and bone volume in normal rats. The cloning of OCIF cDNA revealed that OCIF is a soluble member of the tumor necrosis factor receptor (TNFR) superfamily consisting of four cystein-rich domains, two death domain homologous regions (DDHs), and C-terminal basic domain. Mutational analysis of OCIF revealed that N-terminal portion of OCIF consisting of four cystein-rich domains is sufficient to inhibit osteoclastogenesis. OCIF inhibits osteoclastogenesis by binding to the sites expressed on osteoblastic cells and interrupting cell-to-cell signaling between osteoblastic cells and osteoclast progenitors.