Drug Design, Development and Therapy (Aug 2022)
Corosolic Acid Protects Rat Chondrocytes Against IL-1β-Induced ECM Degradation by Activating Autophagy via PI3K/AKT/mTOR Pathway and Ameliorates Rat Osteoarthritis
Abstract
Hui Han,1– 3,* Ming Chen,2,* Zhenyu Li,2,* Siqi Zhou,2 Yingbin Wu,3 Jian Wei1 1Department of Sports Medicine and Joint Orthopedics, Liuzhou People’s Hospital, Liuzhou, Guangxi, People’s Republic of China; 2Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Department of Orthopedic Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian Wei, Department of Sports Medicine and Joint Orthopedics, Liuzhou People’s Hospital, Liuzhou, Guangxi, People’s Republic of China, Tel +86-13669663233, Email [email protected]: Osteoarthritis (OA) is an age-related degenerative disease associated with enhanced degradation of extracellular matrix (ECM) and decreased autophagy. Our study is aimed to explore how corosolic acid (CRA) affect cartilage ECM metabolism and the potential mechanism.Methods: Rat chondrocytes were pretreated with different concentrations of CRA (0, 2.5, 5, and 10 μM), and were stimulated with IL-1β (10ng/mL) for 24 h, subsequently. RT-qPCR, Western blot, and immunofluorescence were used to detect the expression of genes related to ECM metabolism and explore the potential molecular mechanism. The effect of CRA on articular cartilage was observed in the surgically induced OA rat model with the method of Safranin O/Fast green and immunohistochemical staining.Results: Results showed that CRA reversed the IL-1β-induced degradation of aggrecan and type II collagen and the high expression of MMP13 and ADAMTS5. Mechanistically, CRA enhanced autophagy through inhibiting the classical PI3K/AKT/mTOR signaling pathway. Furthermore, inhibition of autophagy partly abolished the protective effects of CRA on ECM synthesis in IL-1β-treated chondrocytes. Correspondingly, the protective effect of CRA was also confirmed in a rat OA model.Conclusion: Herein, we demonstrate that CRA can enhance autophagy by inhibiting PI3K/AKT/mTOR signaling pathway, prevent IL-1β-induced cartilage ECM degradation, and may be a potentially applicable candidate for the treatment of OA.Keywords: osteoarthritis, corosolic acid, autophagy, extracellular matrix, PI3K/AKT/mTOR signaling
