HMGB1 and rheumatoid arthritis: GRP43/FFA2R is expressed on RA FLSs and upregulated in response to TNFα stimulation, and its inhibition of GPR43 can significantly inhibit a variety of biological mediators and signaling pathways in RA, including IL-6, IL-8, high mobility group protein 1 (HMG-1), monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), and vascular cellular adhesion molecule 1 (VCAM-1), production of ROS and 4-hydroxynoneal, MMP-3, and MMP-13, and activation of the NF-κB inflammatory signaling pathway (163).