The protective role of autophagy in experimental osteoarthritis, and the therapeutic effects of Torin 1 on osteoarthritis by activating autophagy

BMC Musculoskeletal Disorders

Research Article

Ai Guo¹  Ni-Tao Cheng¹  Hai Meng¹ 

[1] Beijing Friendship Hospital, Capital Medical University, Beijing, China;

关键词: Autophagy;    Osteoarthritis;    Cartilage degeneration;    Torin 1;    Protective role;   

DOI  :  10.1186/s12891-016-0995-x

 received in 2015-12-11, accepted in 2016-03-23,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundRecent studies have shown that autophagy was associated with the development of osteoarthritis (OA), the purpose of this research was to determine the exact role of autophagy in OA and investigate effective therapeutic drugs to inhibit the pathological progression of OA.MethodsIn this study, a cellular OA model was generated by stimulating SW1353 cells with IL-1β and a rabbit OA model was established by intra-articular injection of collagenase, followed by treatment with Torin 1 or 3-Methyladenine (3-MA). The mRNA expression levels of VEGF, MMP-13 and TIMP-1 were determined by quantitative real-time PCR. The caitilage degeneration was examined by histological evaluation, chondrocytes degeneration and autophagosomes were observed by transmission electron microscopy. Expression levels of Beclin-1 and LC3 were evaluated by western blotting and immunofluorescence.ResultsThe degeneration of SW 1353 cells, cartilage and chondrocytes was related to the loss of autophagy in experimental OA. 3-MA increased the severity of degeneration of cells and cartilage by autophagy inhibition, while Torin 1 reduced that by autophagy activation.ConclusionsThe loss of autophagy is linked with the experimental OA and autophagy may play a protective role in the pathogenesis of OA. Treatment of Torin 1 can inhibit the degenerative changes of experimental OA by activating autophagy and it may be a useful therapeutic drug for OA.

【 授权许可】

CC BY   
© Cheng et al. 2016