The regulation of osteoarthritis pathogenesis by STING

Abstract

Osteoarthritis (OA) is the most prevalent degenerative disease, which is characterized by cartilage destruction, osteophyte formation, and synovitis. Despite large socioeconomic burden, there is no effective disease-modifying treatment to date. Aging and metabolic disorders such as obesity are one of the risk factors for OA, causing genome instability in the cell with cellular senescence. The accumulation of damaged DNA in the cytosol is one of the pathological factors for OA by inducing innate immune reactions such as inflammation. A cytosolic DNA sensor, the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING), participates in DNA damage responses and acts as an adaptor protein in the immune system. Therefore, this study investigated the role of STING in OA pathogenesis through in vitro and in vivo experiments. STING was upregulated in mouse chondrocytes under various OA pathological conditions and in human and mouse OA cartilage. Loss-of-function studies revealed that deficiency of STING (Sting-/-) in mice ameliorated post-traumatic OA cartilage destruction. In conclusion, this study proposes that STING promotes OA and the inhibition of STING may have a protective role in OA pathogenesis.