HMGB1 and arthritic joint disease: The following observations support a pathogenic role for HMGB1 in RA: aberrant extranuclear HMGB1 expression occurs in the serum, synovial tissue, and synovial fluid of RA patients; aberrant synovial HMGB1 expression is downregulated by intra-articular corticosteroid injections; intraarticular injection of exogenous HMGB1 induces destructive arthritis in mice; HMGB1-targeted treatment attenuates arthritis in animal models and in particular ameliorates the structural damage [6–9].