CD40 ligation of RA synovial fibroblasts by activated T cells activates, in addition to the NF-κB signaling pathway, extracellular-signal-regulated kinase (ERK)-1/2 and p38 mitogen-activated protein kinase (MAPK), upregulates receptor activator of NF-κB ligand (RANKL) expression and enhances osteoclastogenesis [55]. The gene discussed is CD40; the disease is rheumatoid arthritis.