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Effects of TNF on bone metabolism in rheumatoid arthritis. (A) TNF directly promotes osteoclast differentiation; (B) TNF stimulates RANKL production by osteoblasts, fibroblasts and T cells, thus enhancing osteoclast proliferation; (C) TNF stimulates DKK-1 production by synovial fibroblasts, thus inhibiting osteoblast proliferation. DKK-1, Dickkopf WNT Signaling Pathway Inhibitor 1; RANKL, receptor activator of the NFkappaB ligand; TNF, tumour necrosis factor.
