Drug screening for treating osteoarthritis through regulation of Wnt signaling

Abstract

catabolic factors influenced the expressions of Ogg1 and 8-oxoguanine in OA chondrocytes and analysed the relationships among cellular functions, apoptosis and Ogg1 or 8-oxoguanine expression in human chondrocytes. Results: Increased levels of 8-oxoguanine and decreased levels of Ogg1 were observed in OA chondrocytes compared with normal chondrocytes in OA rabbits as well as patients with OA. Decreased expression of Ogg1, but increased expression of 8-oxoguanine, were observed in chondrocytes treated with OA-related catabolic factors. Ogg1 silencing using short hairpin RNAs reduced the chondrocyte activity and augmented chondrocyte apoptosis. Conclusions: Accumulation of 8-oxoguanine, an oxidized form of guanine, and downregulation of its repair enzyme Ogg1 in degenerated articular cartilage may be involved in the pathogenesis of OA. Our findings suggest that Ogg1 protects against catabolic stress-induced chondrocyte dysfunction and apoptosis in OA.