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. 2019 Jan;9(1):a031245. doi: 10.1101/cshperspect.a031245

Figure 3.

Figure 3.

The mechanism of bone destruction in rheumatoid arthritis (RA). RA bone destruction happens in inflamed synovium at the interface of the immune system and bone. The interleukin (IL)-17 produced by T helper (Th)17 cells up-regulates receptor activator of nuclear factor (NF)-κB ligand (RANKL) expression on synovial fibroblasts and induces inflammatory cytokines such as tumor necrosis factor (TNF)-α, IL-6, and IL-1 from synovial macrophages. RANKL expression on synovial fibroblasts is further up-regulated by these cytokines activating osteoclast precursor cells. The immunoglobulin (Ig)G immune complex directly promotes osteoclast differentiation. RANKL stimulates osteoclastic bone resorption, although the Dickkopf-1 (DKK-1) induced by inflammatory cytokines such as TNF-α suppresses bone formation.