RANKL and osteoclast formation

RANKL is a potent inducer of osteoclast formation. Osteotropic factors, 1,25D₃, PTH, PGE₂, and IL-11, induce osteoclast formation by upregulating expression of RANKL on the surface of marrow stromal cells and immature osteoblasts. RANKL then binds its receptor, RANK, on the surface of osteoclast precursors and signals through the NF-κB and JNK pathways to induce osteoclastogenesis and promote osteoclast survival. In addition to RANK, a decoy receptor, OPG/OCIF, inhibits RANKL binding to RANK. RANKL can also occur in a soluble form produced by T cells in inflammatory states. The ratio of RANKL to OPG determines the level of osteoclastogenesis.