The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint
| Autor: | Alberto Centeno, Jesús Loureiro, Rosa Meijide-Faílde, Francisco J. Blanco, Olalla Ramil-Gómez, Marta N. Valcárcel-Ares, Laura Hermida-Carballo, Carlos Vaamonde-García, María J. López-Armada, Romina R. Riveiro-Naveira |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Mitochondrial ROS Cartilage Articular Pathology lcsh:Diseases of the musculoskeletal system Oligomycin Knee Joint Chemokine CXCL1 Fluorescent Antibody Technique Osteoarthritis Mitochondrion medicine.disease_cause Injections Intra-Articular chemistry.chemical_compound 0302 clinical medicine Medicine Orthopedics and Sports Medicine Enzyme Inhibitors Aged 80 and over Synovial Membrane Middle Aged Mitochondrial Proton-Translocating ATPases Immunohistochemistry Mitochondria medicine.anatomical_structure Female medicine.symptom Synovial tissue Research Article musculoskeletal diseases medicine.medical_specialty NF-E2-Related Factor 2 Antigens Differentiation Myelomonocytic Inflammation Electron Transport Complex IV 03 medical and health sciences Rheumatology Antigens CD Internal medicine Animals Humans Interleukin 8 Rats Wistar Aged 030203 arthritis & rheumatology Aldehydes business.industry Macrophages Interleukin-8 medicine.disease Arthritis Experimental Rats 030104 developmental biology Endocrinology Cartilage chemistry Oxidative stress Oligomycins lcsh:RC925-935 Synovial membrane business Reactive Oxygen Species |
| Zdroj: | BMC Musculoskeletal Disorders RUC. Repositorio da Universidade da Coruña instname BMC Musculoskeletal Disorders, Vol 18, Iss 1, Pp 1-12 (2017) |
| Popis: | [Abstract] Background. Recent findings support a connection between mitochondrial dysfunction and activation of inflammatory pathways in articular cells. This study investigates in vivo in an acute model whether intra-articular administration of oligomycin, an inhibitor of mitochondrial function, induces an oxidative and inflammatory response in rat knee joints. Methods. Oligomycin was injected into the rat left knee joint on days 0, 2, and 5 before joint tissues were obtained on day 6. The right knee joint served as control. Results were evaluated by macroscopy and histopathology and by measuring cellular and mitochondrial reactive oxygen species (ROS), 4-hydroxy-2-nonenal (4-HNE, a marker of lipid peroxidation), nuclear factor erythroid 2-related factor 2 (Nrf2), and CD68 (macrophages) and chemokine levels. The marker of mitochondrial mass COX-IV was also evaluated. Results. The macroscopic findings showed significantly greater swelling in oligomycin-injected knees than in control knees. Likewise, the histological score of synovial damage was also increased significantly. Immunohistochemical studies showed high expression of IL-8, coinciding with a marked infiltration of polymorphonuclears and CD68+ cells in the synovium. Mitochondrial mass was increased in the synovium of oligomycin-injected joints, as well as cellular and mitochondrial ROS production, and 4-HNE. Relatedly, expression of the oxidative stress-related transcription factor Nrf2 was also increased. As expected, no histological differences were observed in the cartilage; however, cytokine-induced neutrophil chemoattractant-1 mRNA and protein expression were up-regulated in this tissue. Conclusions. Mitochondrial failure in the joint is able to reproduce the oxidative and inflammatory status observed in arthritic joints. Instituto de Salud Carlos III; 09/02340 Instituto de Salud Carlos III, RD12/0009/0018, RIER Galicia. Consellería de Innovación, Industria e Comercio; PXIB916357PR Instituto de Salud Carlos III; PI12/02771 Xunta de Galicia; PS09/56 Galicia. Consellería de Economía e Industria; INCITE 09E1R916139ES Galicia. Consellería de Economía e Industria; IN845B2010/176 Galicia. Consellería de Economía e Industria; 10CSA916035PR |
| Databáze: | OpenAIRE |
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