Abstract
Reduced autophagy has been implied in chondrocyte death and osteoarthritis. Curcumin (Cur) owns therapeutic effect against osteoarthritis (OA) and enhances autophagy in various tumor cells. Whether the cartilage protection of curcumin is associated with autophagy promotion and the potential signaling pathway involved remains unclear. The present study aimed to investigate the role of autophagy in the anti-OA activity of curcumin using spontaneous and surgically induced OA mice model. Spontaneous and surgically induced OA mice model was established and treated with Cur. Articular cartilage destruction and proteoglycan loss were scored through Safranin O/Fast green staining. Apoptotic cell death was detected with TUNEL (terminal deoxynucleotidyl transferase-mediated dTUP-biotin nick end labeling assay) staining and Western blot for caspase-3, Bcl-2 associated X protein (Bax), and Bcl-2 (B-cell lymphoma-2). Light chain 3 (LC3) immunohistochemistry was used to evaluate autophagy. In vitro, primary chondrocytes were treated with interleukin 1 beta (IL-1β) and Cur. Autophagy was inhibited using 3-methyladenine. Apoptosis and autophagy were detected using flow cytometry and Western blotting assay. Curcumin treatment enhanced autophagy, reduced apoptosis, and cartilage loss in both OA models. In vitro, curcumin treatment improved IL-1β induced autophagy inhibition, cell viability decrease, and apoptosis. Mechanistically, in vivo studies suggested curcumin promoted autophagy through regulating Akt/mTOR pathway. In conclusion, our results demonstrate that curcumin-induced autophagy via Akt/mTOR signaling pathway contributes to the anti-OA effect of curcumin.
Highlights
Osteoarthritis (OA) is a degenerative and progressive disease with substantial pain and disability in worldwide
The results showed that expression level of cleaved caspase-3 and B-cell lymphoma-2 (Bcl-2) associated X protein (Bax)/Bcl2 was significantly lower with curcumin treatment in IL-1β-treated cells (P
Our result demonstrated that mRNA expression of MMP13 and ADAMTS-5 was decreased, while Co12a1 and Aggrecan expression was increased with curcumin treatment in cells co-treated with IL-1β (P
Summary
Osteoarthritis (OA) is a degenerative and progressive disease with substantial pain and disability in worldwide. Life lived with disability (YLDs) for hip and knee OA increased from 10.5 million in 1990 to 17.1 million in 2010 [1]. It is characterized by inflammation of synovial membrane, modification of the subchondral bone structure, degradation of articular cartilage which is often reflected by loss of cartilage extracellular matrix, and reduced cartilage cellularity [2,3]. Despite the great attempts made on reducing the prevalence of OA, there is no effective treatment or cure that reverses disease progression [4]. Novel and safe treatment for OA are in high demand and are subject of the present study
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