title: Hypoxia protects articular chondrocytes from thapsigargin-induced apoptosis.
abstract: The present study investigates the effect of low oxygen concentrations on thapsigargin-induced apoptosis and reactive oxygen species (ROS)-related signaling in articular chondrocytes. Chondrocytes were obtained from normal canine knee cartilage and were treated with different concentrations of thapsigargin for 24h under normoxic (21% oxygen tension) or hypoxic (1% oxygen tension) conditions. The cells treated with thapsigargin under normoxic conditions showed a dose-dependent induction of apoptosis. However, the cellular changes and apoptotic events that occurred following thapsigargin treatment, were completely inhibited by hypoxia, including loss of mitochondrial transmembrane potential (MTP), ROS generation and JNK phosphorylation. Moreover, the cells exposed to hypoxic conditions showed increased expression of the anti-apoptotic proteins xIAP-2 and Bcl-2. We demonstrate that hypoxia inhibited thapsigargin-induced apoptosis in chondrocytes by regulating ROS-related signaling and the expression of anti-apoptotic proteins. We propose that maintaining hypoxic conditions in articular cartilage may be required for the prevention of chondrocyte and cartilage diseases such as arthritis.
authors.affiliation: Center for Healthcare Technology Development, Bio-Safety Research Institute, Chonbuk National University, Jeonju, Jeonbuk, South Korea.
authors.forename: Atul A
authors.initials: AA
authors.lastname: Chaudhari
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Seol
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Dai-Wu
authors.initials: DW
authors.lastname: Seol
authors.forename: Sang-Youel
authors.initials: SY
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051636:X-Linked Inhibitor of Apoptosis Protein; D019284:Thapsigargin; D048670:MAP Kinase Kinase 4; D010100:Oxygen