Journal of Inflammation Research (Jul 2021)
Quercetin Alleviates Osteoarthritis Progression in Rats by Suppressing Inflammation and Apoptosis via Inhibition of IRAK1/NLRP3 Signaling
Abstract
Wenjun Li,1 Yeyang Wang,1 Yaqin Tang,2 Hanyu Lu,1 Yong Qi,1 Guitao Li,1 Hebei He,1 Fanglian Lu,1 Yixin Yang,1 Hongtao Sun1 1Department of Orthopedics, Guangdong Second Provincial General Hospital, Guangzhou, 510317, Guangdong Province, People’s Republic of China; 2Department of Internal Medicine, The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and Pharmacology, Guangzhou, Guangdong Province, 510405, People’s Republic of ChinaCorrespondence: Hongtao SunDepartment of Orthopedics, 12th Floor, Building 3, Guangdong Second Provincial General Hospital, 466 Xingang Zhong Road, Haizhu District, Guangzhou, 510317, Guangdong Province, People’s Republic of ChinaTel +86 13808849918Email [email protected] LuDepartment of Orthopedics, 12th Floor, Building 3, Guangdong Second Provincial General Hospital, 466 Xingang Zhong Road, Haizhu District, Guangzhou, Guangdong Province, 510317, People’s Republic of ChinaTel +86 18925077162Email [email protected]: Quercetin was recently reported to help protect against osteoarthritis (OA) progression, but the molecular mechanism for that protective affect remains unclear.Methods: Here, OA model rats were intraperitoneally injected with quercetin, and the severity of cartilage damage in the rats was evaluated by H&E, Safranin O, and Toluidine blue, as well as by using the Osteoarthritis Research Society International (OARSI) Scoring System. Additionally, rat chondrocytes were treated with quercetin and then stimulated with IL-1β. The levels of pro-inflammatory cytokines (IL-1β, IL-18, and TNF-α) were detected by ELISA.Cell apoptosis was evaluated by flow cytometry and Hoechst staining. ROS levels were measured using a DCFH-DA probe. Protein expression was evaluated by Western blotting, immunohistochemical staining, and immunofluorescence. Results: Our data showed that quercetin attenuated the degeneration and erosion of articular cartilage, suppressed inflammation and apoptosis, and downregulated the levels of IRAK1, NLRP3, and caspase-3 expression. In vitro data showed that overexpression of NLRP3 could reverse the suppressive effect of quercetin on IL-1β-induced rat chondrocyte injuries. Importantly, rescue experiments confirmed that quercetin inhibited IL-1β-induced rat chondrocyte injuries in vitro by suppressing the IRAK1/NLRP3 signaling pathway.Conclusion: Our study indicated that quercetin inhibits IL-1β-induced inflammation and cartilage degradation by suppressing the IRAK1/NLRP3 signaling pathway.Keywords: quercetin, osteoarthritis, IRAK1, NLRP3, inflammation, apoptosis
