Immune function of the decoy receptor osteoprotegerin

Osteoprotegerin (OPG) is a member of the tumor necrosis factor receptor (TNFR) superfamily. OPG has an important function as a protector of bone, demonstrated by the fact that OPG(-/-) mice have severe osteoporosis. OPG acts as a decoy receptor, binding to RANK ligand (RANKL), thus preventing the interaction between receptor activator of NF-kappaB (RANK) and RANKL. This interaction is required for the development of functionally active osteoclasts. Osteoclasts are cells of the monocytic lineage that are responsible for bone resportion. Furthermore, as well as being an important player in the regulation of bone metabolism, OPG also has a role in the regulation of the immune response. Dendritic cells (DCs) express RANK and T cells express RANKL. The ligation of RANK by RANKL can activate both T cells and DCs. Furthermore, both B cells and DCs secrete OPG, and this secretion is regulated by the CD40 receptor. OPG(-/-) mice have B-cell developmental defects. Also, DCs isolated from OPG(-/-) mice more efficiently present antigen in vitro and secrete elevated amounts of inflammatory cytokines when stimulated with bacterial products, or soluble RANKL in vitro. Taken together, this suggests that OPG plays an important role in the immune response regulating the interactions between T cells and DCs.