In addition to the direct effects of EGFR signaling on osteoclasts, several studies have also indicated that in rheumatoid arthritis (RA), EGFR ligands, such as EGF and TGF-α, induce RA synovial fibroblasts to produce various pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), thereby further activating osteoclast precursor cells (monocytes/macrophages), promoting osteoclastogenesis, and ultimately leading to bone erosion 48, 49. This evidence concerns the gene EGF and rheumatoid arthritis.