Figure 1.

Osteoblast-derived RANKL binds to RANK on monocytes to differentiate them into mature osteoclasts. Osteoblast-derived RANKL plays important role in generating osteoclast in physiological condition. However, immune cell and FLS-derived RANKL play pathogenic role in RA. Proinflammatory cytokines such as IL-1 and TNFα effectively stimulate osteoblast to express RANKL. FLS-derived RANKL enhances osteoclastogenesis in RA joints. RANK: receptor activator of the nuclear factor kappa B; RANKL: receptor activator of the nuclear factor kappa B ligand; FLS: fibroblast like synoviocyte; RA: rheumatoid arthritis; IL-1: Interleukin-1; TNFα: tumor necrosis factor-alpha.