Fatty acid sensing GPCR (GPR84) signaling safeguards cartilage homeostasis and protects against osteoarthritis

摘要: It is well known that free fatty acids (FFAs) have beneficial effects on the skeletal system, however, which acid sensing GPCR(s) and how regulating cartilage development osteoarthritis (OA) pathogenesis largely unknown. In this study, we found Gpr84, a receptor for medium-chain FFAs (MCFA), was only FFA-sensing GPCR in human mouse chondrocytes exhibited elevated expression when stimulated by interleukin (IL)-1β. Gpr84-deficiency upregulated catabolic regulator downregulated anabolic factor IL-1β-induced cell model destabilization of medial meniscus (DMM)-induced OA model. Gpr84-/- mice an aggravated phenotype characterized severe degradation, osteophyte formation subchondral bone sclerosis. Moreover, activating Gpr84 directly enhanced extracellular matrix (ECM) generation while knockout suppressed ECM-related gene expression. Especially, agonists GPR84 protected explants against degeneration inducing At molecular level, activation inhibited NF-κB signaling pathway. Furthermore, deletion had little effect articular spine cartilaginous tissues during growth. Together, all our results demonstrated (Gpr84) played critical role pathogenesis, or MCFA supplementation has potential preventing progression without side effect.