Fig. 1.

Chronic inflammation and the development of erosions. In the presence of synovitis several cells including T- and B-lymphocytes, synovial fibroblasts, and osteoblasts express RANKL (Receptor activator of nuclear factor kappa-Β ligand). RANKL binds to RANK (Receptor activator of nuclear factor kappa-Β) and promotes osteoclast differentiation and activity. TNFα and other proinflammatory cytokines stimulate osteoclast activity directly and indirectly through stimulation of T cells and increased RANKL production. TNFα reduces bone formation by (a) inducing Dickkopf 1 (Dkk-1), which blocks the differentiation of osteoprogenitor cells into osteoblasts and (b) inducing the expression of sclerostin in osteocytes, which is a potent downregulator of osteoblast differentiation and activity Anti-citrullinated protein antibodies (ACPA) bind to inflammatory cells (macrophages) and propagate inflammation and can stimulate osteoclasts directly through FC receptors