title: Non-dioxin-like polychlorinated biphenyls (PCB 101, PCB 153 and PCB 180) induce chondrocyte cell death through multiple pathways.
abstract: Environmental pollutants are known to have adverse effects on human health. However, the link between chemical exposure and osteoarthritis remains little investigated. This study sought to assess in vitro the effect of several non-dioxin-like polychlorinated biphenyls (NDL-PCBs) on chondrocytes viability and apoptosis induction. Murine chondrogenic ATDC-5 cell line and human T/C-28a2 immortalized chondrocytes were exposed to NDL-PCBs 101, 153 and 180. Cell viability was examined using MTT assay. Necrosis was evaluated by LDH assay. Expression of apoptotic related proteins, such as caspase-3, Bcl-2 and Bax was assessed by Western blot analysis. Finally, oxidative stress was evaluated by malondialdehyde (MDA) assay and the Oxidative Stress Index. In vitro exposure to NDL-PCBs caused strong reduction of cell viability in a concentration-dependent manner. Data from LDH assay showed cellular necrosis induction. Caspase-3 activation, as well as, altered Bcl2/Bax ratio and p38 MAP-kinase phosphorylation also suggested apoptosis induction. Finally, MDA levels and Oxidative Stress Index revealed that PCBs drive chondrocyte death via increase of oxidative stress. The viability of murine and human chondrocytes was reduced in presence of PCBs. The activity of PCBs on cell viability is likely to be mediated by complex alterations involving regulation mechanisms of apoptosis, necrosis and oxidative stress.
authors: SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain; Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña (UDC), Campus de A Coruña, 15071 A Coruña, Spain.
authors: Vanessa
authors: V
authors: Abella
authors: University of Naples Federico II, Dept. of Pharmacy, 80138 Naples, Italy.
authors: Anna
authors: A
authors: Santoro
authors: SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain.
authors: Morena
authors: M
authors: Scotece
authors: SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain.
authors: Javier
authors: J
authors: Conde
authors: SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain.
authors: Verónica
authors: V
authors: López-López
authors: University of Catanzaro "Magna Grecia", Dept. of Health Science, 88100 Catanzaro, Italy.
authors: Veronica
authors: V
authors: Lazzaro
authors: SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain.
authors: Juan Jesus
authors: JJ
authors: Gómez-Reino
authors: University of Naples Federico II, Dept. of Pharmacy, 80138 Naples, Italy.
authors: Rosaria
authors: R
authors: Meli
authors: SERGAS, Research Laboratory 9, NEIRID Lab (Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases), Institute of Medical Research (IDIS), Santiago University Clinical Hospital, 15706 Santiago de Compostela, Spain. Electronic address: oreste.gualillo@sergas.es.
authors: Oreste
authors: O
authors: Gualillo
mesh_terms: D000818:Animals; D053148:Caspase 3 / Q000032:analysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004785:Environmental Pollutants / Q000633:toxicity*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008315:Malondialdehyde / Q000032:analysis; D051379:Mice; D010003:Osteoarthritis / Q000209:etiology*; D018384:Oxidative Stress / Q000187:drug effects*; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D004785:Environmental Pollutants; D051028:bcl-2-Associated X Protein; D008315:Malondialdehyde; D011078:Polychlorinated Biphenyls; D007770:L-Lactate Dehydrogenase; D048051:p38 Mitogen-Activated Protein Kinases; D053148:Caspase 3
keywords: Apoptosis; Chondrocytes; Necrosis; Non-dioxin-like PCBs; Oxidative stress