In conclusion,HMGB1 acts in synergy with LPS to upregulate TLR4 and RAGEexpression on the surface of SF in RA and then to augment IL-6,MMP-3, and MMP-13 production, which depends on p38 MAPK and NF-κBactivation. The gene discussed is HMGB1; the disease is rheumatoid arthritis.