title: The dual role of autophagy in chondrocyte responses in the pathogenesis of articular cartilage degeneration in osteoarthritis.
abstract: The present study aimed to analyze the responses to autophagy in osteoarthritis (OA) and aging chondrocytes in order to elucidate the role of autophagy in the pathogenesis of OA. We used multiple assays to confirm that autophagic activity was downregulated in chondrocytes of aged articular cartilage. Surprisingly, we found that the expression of autophagy-related proteins was not decreased in the tissues of patients with OA. We also observed that rapamycin-induced autophagy prevented the accumulation of subdiploid cells in young chondrocytes, while it induced cell death by autophagy in OA chondrocytes. Our results demonstrate that autophagic activity decreases with aging, and may be responsible for the cytoprotective effects in young cartilage. However, we found that autophagic activity in patients with OA was higher than in the aging group, and reported autophagic cell death in OA chondrocytes. These results suggest that autophagy plays both a cytoprotective and death-promoting role in the pathogenesis of OA.
authors.affiliation: Department of Orthopaedics, Anhui Geriatric Institute, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Mingli
authors.initials: M
authors.lastname: Wang
authors.forename: Zongsheng
authors.initials: Z
authors.lastname: Yin
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000368:Aged; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D002453:Cell Cycle / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D020123:Sirolimus / Q000494:pharmacology; D055815:Young Adult
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; C025946:3-methyladenine; D000225:Adenine; D020123:Sirolimus