Schematic representation of the mechanism of action of a, pro-resorptive and calcitropic factors; and b, anabolic and anti-osteoclastic factors. RANKL expression is induced in osteoblasts, activated T cells, synovial fibroblasts and bone marrow stromal cells, and subsequently binds to its specific membrane-bound receptor RANK, thereby triggering a network of TRAF-mediated kinase cascades that promote osteoclast differentiation, activation and survival. Conversely, OPG expression is induced by factors that block bone catabolism and promote anabolic effects. OPG binds and neutralizes RANKL, leading to a block in osteoclastogenesis and decreased survival of pre-existing osteoclasts.

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