Quercetin attenuates oxidative stress-induced apoptosis via SIRT1/AMPK-mediated inhibition of ER stress in rat chondrocytes and prevents the progression of osteoarthritis in a rat model

Apoptosis of chondrocytes are the main initiator of osteoarthritis (OA) and can be explained by oxidative stress and endoplasmic reticulum (ER) stress, thus the pharmacological interventions aimed at inhibiting of these pathways may be a promising approach for the management of OA. Quercetin is a member of the flavonoid family and has antioxidant and anti-inflammatory properties in degenerative diseases. However, its effects and potential mechanisms on the pathological process of OA are not very clear. The present study aimed to investigate the protective effects of quercetin on OA and the underlying mechanisms. The tert-butyl hydroperoxide (TBHP)-stimulated rat chondrocytes and destabilization of the medial meniscus OA rat model was used to explore the protective effects of quercetin. Our results showed thatquercetin treatment can attenuate oxidative stress, ER stress, and associated apoptosis. Moreover,quercetin inhibited ER stress through activating the sirtuin1/adenosine monophosphate-activated protein kinase (SIRT1/AMPK) signaling pathway. The protective effects ofquercetin were also observed in OA rat model which is evidenced by abolished cartilage degeneration and decreased chondrocytes apoptosis in the knee joints. Our results suggested thatquercetin is a promising treatment for OA.