title: Autophagy Protects Advanced Glycation End Product-Induced Apoptosis and Expression of MMP-3 and MMP-13 in Rat Chondrocytes.
abstract: Aging is one of the most prominent risk factors for the pathological progression of osteoarthritis (OA). One feature of age-related changes in OA is advanced glycation end products (AGEs) accumulation in articular cartilage. Autophagy plays a cellular housekeeping role by removing dysfunctional cellular organelles and proteins. However, the relationship between autophagy and AGE-associated OA is unknown. The aim of this study is to determine whether autophagy participates in the pathology of AGE-treated chondrocytes and to investigate the exact role of autophagy in AGE-induced cell apoptosis and expression of matrix metalloproteinase- (MMP-) 3 and MMP-13. AGEs induced notable apoptosis that was detected by Annexin V/PI double-staining, and the upregulation of MMP-3 and MMP-13 was confirmed by Western blotting. Autophagy-related proteins were also determined by Western blotting, and chondrocytes were transfected with mCherry-GFP-LC3B-adenovirus to monitor autophagic flux. As a result, autophagy significantly increased in chondrocytes and peaked at 6 h. Furthermore, rapamycin (RA) attenuated AGE-induced apoptosis and expression of MMP-3 and MMP-13 by autophagy activation. In contrast, pretreatment with autophagy inhibitor 3-methyladenine (3-MA) enhanced the abovementioned effects of AGEs. We therefore demonstrated that autophagy is linked with AGE-related pathology in rat chondrocytes and plays a protective role in AGE-induced apoptosis and expression of MMP-3 and MMP-13.
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Wenzhou
authors.identifier: 0000-0001-5879-9482
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Peng
authors.identifier: 0000-0002-4317-9755
authors.initials: P
authors.lastname: Ao
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Jian
authors.identifier: 0000-0001-7566-2613
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Tianlong
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Libiao
authors.identifier: 0000-0001-9941-9837
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Zhongbo
authors.identifier: 0000-0001-7863-2479
authors.initials: Z
authors.lastname: Deng
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Wenjie
authors.identifier: 0000-0001-5970-3569
authors.initials: W
authors.lastname: Chen
authors.affiliation: Jiujiang University, Key Laboratory of Medical Transformation of Jiujiang, Jiujiang, Jiangxi 332000, China.
authors.forename: Changchang
authors.identifier: 0000-0001-7999-0104
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China.
authors.forename: Xigao
authors.identifier: 0000-0002-6105-1499
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000201:enzymology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D053509:Matrix Metalloproteinase 13 / Q000096:biosynthesis*; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D017127:Glycation End Products, Advanced; D053509:Matrix Metalloproteinase 13; C507083:Mmp13 protein, rat; D019278:Matrix Metalloproteinase 3