Damage-associated molecular patterns in the pathogenesis of osteoarthritis: potentially novel therapeutic targets
We investigated the expression and localization of high-mobility group box chromosomal protein-1 (HMGB-1) in human osteoarthritic (OA) cartilage in relation to the histopathological grade of cartilage destruction, and examined the role of HMGB-1 in the regulation of proinflammatory cytokine expression in chondrocytes. An immunohistochemical study demonstrated that total HMGB-1-positive cell ratios increase as the Osteoarthritis Research Society International (OARSI) histological grade increased. The population of cytoplasmic HMGB-1-positive chondrocytes was especially increased in the deep layers of higher-grade cartilage. The ratios and localization of receptors for advanced glycation end products (RAGE) expression by chondrocytes in Grade 2, 3, and 4 were significantly higher than those in Grade 1. In vitro stimulation with IL-1β, but not TNFα, significantly upregulated the expression of HMGB-1 mRNA by human OA chondrocytes. Both IL-1β and TNFα promoted the translocation of HMGB-1 from nuclei to cytoplasm. IL-1β and TNFα secretions were stimulated at higher levels of HMGB-1. The results of our study suggest the involvement of HMGB-1 in the pathogenesis of cartilage destruction in OA.