Investigations suggest that CCN2 acts synergistically with macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kappa B ligand (RANKL) to promote osteoclastogenesis and that excessive CCN2 production by RA synovial fibroblasts (RASFs) enhances osteoclastic function through integrin αVβ3-mediated pathways such as FAK and ERK1/2 phosphorylation [36]. Here, TNFSF11 is linked to rheumatoid arthritis.