OSTEOCLAST DIFFERENTIATION FACTOR MEDIATES AN ESSENTIAL SIGNAL FOR BONE-RESORPTION INDUCED BY 1-ALPHA-25-DIHYDROXYVITAMIN D-3, PROSTAGLANDIN E-2, OR PARATHYROID-HORMONE IN THE MICROENVIRONMENT OF BONE

Osteoclast differentiation factor (ODF), a ligand for osteoprotegerin (OPG)/osteoclastogenesis-inhibitory factor (OCIF), induces osteoclast- like cell formation in vitro. To elucidate the role of ODF in the micr oenvironment of bone, we examined effects of ODF, OPG/OCIF, and anti-O DF polyclonal antibody on bone resorption using a fetal mouse long bon e culture system. A genetically engineered soluble-form ODF (sODF) eli cited bone resorption in a concentration dependent manner and OPG/OCIF blocked the bone resorption. Anti-ODF polyclonal antibody, which neut ralizes ODF activity, negated bone resorption induced by 1 alpha,25-di hydroxyvitamin D-3, parathyroid hormone, or prostaglandin E-2, OPG/OCI F also abolished bone-resorbing activity elicited by these bone-resorb ing agents. Interleukin 1 alpha-stimulated bone resorption was also si gnificantly suppressed by anti-ODF polyclonal antibody and OPG/OCIF. T hus, we conclude that ODF plays a critical role in bone resorption in the microenvironment of bone. (C) 1998 Academic Press.