title: The protective role of autophagy in experimental osteoarthritis, and the therapeutic effects of Torin 1 on osteoarthritis by activating autophagy.
abstract: BACKGROUND
  Recent 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.
  
  
  METHODS
  In 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.
  
  
  RESULTS
  The 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Ni-Tao
authors.initials: NT
authors.lastname: Cheng
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Ai
authors.initials: A
authors.lastname: Guo
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Meng
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D002356:Cartilage / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019610:Cytoprotection; D006801:Humans; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009287:Naphthyridines / Q000494:pharmacology*; D011817:Rabbits; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: C553294:1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one; D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009287:Naphthyridines; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C025946:3-methyladenine; C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13; D000225:Adenine
keywords: Autophagy; Cartilage degeneration; Osteoarthritis; Protective role; Torin 1