Abstract
Osteoclasts play critical roles in bone resorption at the site of inflammatory joints, and receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) are required for osteoclastogenesis. RANKL, a member of tumor necrosis factor (TNF) family cytokine, is critically involved in the differentiation and fusion of precursors into mature osteoclasts. Binding of RANKL to its receptor RANK activates TNF receptor-associated factor 6 (TRAF6), which is linked to the nuclear factor-κB (NF-κB) and/or mitogen-activated protein kinases (MAPKs). Among these signaling molecules, much attention has been raised to MAPKs as the therapeutic targets for bone resorptive diseases. In this review, we summarized the involvement of MAPKs and the studies using the specific inhibitors of MAPKs in osteoclastogenesis. The inhibitor of tumor progression locus 2 (Tpl2) effectively suppressed osteoclastogenesis, suggesting that the blockade of the particular MAPK pathway could be of clinical importance as the treatment option for bone destructive diseases including rheumatoid arthritis.
