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BMC Musculoskelet Disord. 2017 Jun 12;18(1):254. doi: 10.1186/s12891-017-1621-2.

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

Author information

1
Aging and Inflammation Research Lab, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain.
2
Tissue Engineering and Cellular Therapy Group, INIBIC, Department of Medicine, Faculty of Health Sciences- UDC, Campus Oza, A Coruña, Spain.
3
Experimental Surgery Unit, INIBIC-CHUAC, A Coruña, Spain.
4
Osteoarticular and Aging Research Lab, Rheumatology Service, INIBIC, CHUAC, Sergas, UDC, A Coruña, Spain.
5
Aging and Inflammation Research Lab, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC), As Xubias, 15006, A Coruña, Spain. Maria.Jose.Lopez.Armada@sergas.es.

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.

KEYWORDS:

Cartilage; Inflammation; Mitochondria; Oxidative stress; Synovial tissue

PMID:
28606072
PMCID:
PMC5469149
DOI:
10.1186/s12891-017-1621-2
[Indexed for MEDLINE]
Free PMC Article

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