Another example for the coupling of bone formation to resorption is that in addition to increase bone resorption directly independent of RANKL-TRAF6 axis (34, 51, 64) and indirectly by stimulating RANKL production (65), TNF-α exhibits anabolic effect to bone through its polarized macrophage to slow down bone loss in rheumatoid arthritis (35). The gene discussed is TNF; the disease is rheumatoid arthritis.