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Nitric oxide compounds have different effects profiles on human articular chondrocyte metabolism

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dc.contributor.authorde Andrés, María C
dc.contributor.authorManeiro, Emilia
dc.contributor.authorMartín, Miguel A
dc.contributor.authorArenas, Joaquín
dc.contributor.authorBlanco, Francisco J
dc.contributor.funderMinisterio de Ciencia e Innovación (España)
dc.contributor.funderInstituto de Salud Carlos III
dc.contributor.funderUnión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
dc.date.accessioned2017-09-04T16:26:26Z
dc.date.available2017-09-04T16:26:26Z
dc.date.issued2013-09-11
dc.description.abstractINTRODUCTION: The pathogenesis of osteoarthritis (OA) is characterized by the production of high amounts of nitric oxide (NO), as a consequence of up-regulation of chondrocyte-inducible nitric oxide synthase (iNOS) induced by inflammatory cytokines. NO donors represent a powerful tool for studying the role of NO in the cartilage in vitro. There is no consensus about NO effects on articular cartilage in part because the differences between the NO donors available. The aim of this work is to compare the metabolic profile of traditional and new generation NO donors to see which one points out the osteoarthritic process in the best way. METHODS: Human healthy and OA chondrocytes were isolated from patients undergoing joint replacement surgery, and primary cultured. Cells were stimulated with NO donors (NOC-12 or SNP). NO production was evaluated by the Griess method, and apoptosis was quantified by flow cytometry. Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities by enzymatic assay, mitochondrial membrane potential (Δψm) by JC-1 using flow cytometry, and ATP levels were measured by luminescence assays. Glucose transport was measured as the uptake of 2-deoxy-[(3)H]glucose (2-[(3)H]DG). Statistical analysis was performed using the Mann-Whitney U test. RESULTS: NOC-12 liberates approximately ten times more NO2- than SNP, but the level of cell death induced was not as profound as that produced by SNP. Normal articular chondrocytes stimulated with NOC-12 had reduced activity from complexes I, III y IV, and the mitochondrial mass was increased in these cells. Deleterious effects on ΔΨm and ATP levels were more profound with SNP, and this NO donor was able to reduce 2-[(3)H]DG levels. Both NO donors had opposite effects on lactate release, SNP diminished the levels and NOC-12 lead to lactate accumulation. OA chondrocytes incorporate significantly more 2-[(3)H]DG than healthy cells. CONCLUSIONS: These findings suggest that the new generation donors, specifically NOC-12, mimic the OA metabolic process much better than SNP. Previous results using SNP have to be considered prudently since most of the effects observed can be induced by the interactions of secondary products of NO.
dc.description.peerreviewedSí
dc.description.sponsorshipThe authors express appreciation to the Department of Orthopedics and the Tissue Bank of the Complejo Hospitalario Universitario de A Coruña for providing cartilage samples. This study was supported by grants from the Fondo Investigación Sanitaria, Madrid, Spain: (CIBER- CB06/01/0040; PI-12/00329; RETIC-RIER-RD12/0009/0018; and Proteo-Red/ISCIII); Ministerio Ciencia e Innovación, Madrid, Spain: PLE2009-0144 and FEDER (European Community).
dc.format.number5
dc.format.pageR115
dc.format.volume15
dc.identifier.citationArthritis Res Ther. 2013; 15(5): R115
dc.identifier.doi10.1186/ar4295
dc.identifier.e-issn1478-6354
dc.identifier.journalArthritis Research & Therapy
dc.identifier.pubmedID24025112
dc.identifier.urihttp://hdl.handle.net/20.500.12105/4800
dc.language.isoeng
dc.publisherBioMed Central (BMC)
dc.relation.publisherversionhttps://doi.org/10.1186/ar4295
dc.repisalud.centroISCIII::Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)
dc.repisalud.institucionISCIII
dc.rights.accessRightsopen accesses_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectChondrocytes
dc.subjectNitric oxide
dc.subjectApoptosis
dc.subjectMitochondria
dc.subjectGlucose
dc.subjectOsteoarthritis
dc.titleNitric oxide compounds have different effects profiles on human articular chondrocyte metabolism
dc.typeresearch article
dc.type.hasVersionVoR
dspace.entity.typePublication
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Unidad Funcional de Investigación de Enfermedades Crónicas (UFIEC)
i+12 - Instituto de Investigación Hospital 12 de Octubre (Madrid)
INIBIC - Instituto de Investigación Biomédica A Coruña (Galicia)