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BMC Musculoskeletal Disorders
Published in: BMC Musculoskeletal Disorders 1/2017

Open Access 01-12-2017 | Research article

The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint

Authors: Carlos Vaamonde-García, Jesús Loureiro, Marta N. Valcárcel-Ares, Romina R. Riveiro-Naveira, Olalla Ramil-Gómez, Laura Hermida-Carballo, Alberto Centeno, Rosa Meijide-Failde, Francisco J. Blanco, María J. López-Armada

Published in: BMC Musculoskeletal Disorders | Issue 1/2017

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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.
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Metadata
Title
The mitochondrial inhibitor oligomycin induces an inflammatory response in the rat knee joint
Authors
Carlos Vaamonde-García
Jesús Loureiro
Marta N. Valcárcel-Ares
Romina R. Riveiro-Naveira
Olalla Ramil-Gómez
Laura Hermida-Carballo
Alberto Centeno
Rosa Meijide-Failde
Francisco J. Blanco
María J. López-Armada
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Musculoskeletal Disorders / Issue 1/2017
Electronic ISSN: 1471-2474
DOI
https://doi.org/10.1186/s12891-017-1621-2

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