title: Peroxiredoxin 4 inhibits IL-1β-induced chondrocyte apoptosis via PI3K/AKT signaling.
abstract: BACKGROUND
  Chondrocytes apoptosis induced by reactive oxygen species (ROS) plays a critical role in the pathogenesis of osteoarthritis (OA). Peroxiredoxin 4 (PRDX4), a member of the PRDX family, is essential for removing metabolic free radicals and reducing intracellular ROS. In this study, we sought to investigate the roles of PRDX4 on interleukin 1β (IL-1β)-induced chondrocyte apoptosis.
  
  
  METHODS
  Primary chondrocytes were isolated from the articular cartilage of Sprague-Dawley rats, infected with PRDX4 overexpressing lentivirus and treated with IL-1β (10ng/mL). Cell apoptosis and ROS production identified by flow cytometry. Protein expression levels was evaluated by Western blotting analysis. Nitric oxide (NO) production and Caspase-3/9 activation were assessed by the Griess reaction method and colorimetric assay kit, respectively.
  
  
  RESULTS
  PRDX4 overexpression in chondrocytes significantly decreased IL-1β-induced apoptosis. It also reversed the activity of IL-1β that increased ROS and NO production. PRDX4 overexpression reversed the activity of IL-1β that reduced the levels of Bcl-2, p-AKT and p-PRAS40, as well as increased Bax levels and Caspase-3/9 activation. More importantly, pre-treated with AKT inhibitor (AZD5363) significantly reduced the protective effects of PRDX4.
  
  
  CONCLUSIONS
  Our data demonstrated that the regulatory effects of PRDX4 on IL-1β-induced chondrocyte apoptosis can be partially attributed to phosphatidylinositol 3-kinase/AKT signaling. These results indicate that PRDX4 might play a protective role in OA cartilage degeneration.
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 20065, China.
authors.forename: Zhitao
authors.initials: Z
authors.lastname: Rao
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 20065, China. Electronic address: tongjijoint0106@163.com.
authors.forename: Shuqing
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Orthopaedics, Tongji Hospital, Tongji University School of Medicine, Shanghai, 20065, China.
authors.forename: Jiaqi
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002358:Cartilage, Articular / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D019902:Chondrocytes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010003:Osteoarthritis / Q000378:metabolism; D054464:Peroxiredoxins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
chemical_list: D053583:Interleukin-1beta; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D054464:Peroxiredoxins; C515982:Prdx4 protein, rat; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Chondrocytes; IL-1β; Osteoarthritis; PRDX4