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Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation

INTRODUCTION: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular...

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Autores principales: Wann, Angus KT, Mistry, Jiten, Blain, Emma J, Michael-Titus, Adina T, Knight, Martin M
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046514/
https://www.ncbi.nlm.nih.gov/pubmed/21059244
http://dx.doi.org/10.1186/ar3183
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author Wann, Angus KT
Mistry, Jiten
Blain, Emma J
Michael-Titus, Adina T
Knight, Martin M
author_facet Wann, Angus KT
Mistry, Jiten
Blain, Emma J
Michael-Titus, Adina T
Knight, Martin M
author_sort Wann, Angus KT
collection PubMed
description INTRODUCTION: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. METHODS: Two specific n-3 compounds were tested, namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), each at 0.1, 1 and 10 μM. Full thickness bovine cartilage explants, 5 mm in diameter, were cultured for 5 days with or without IL-1β and in the presence or absence of each n-3 compound. The media were replaced every 24 hours and assayed for sGAG content using the 1,9-dimethylmethylene blue (DMB) method. Chondrocyte viability was determined at the end of the culture period using fluorescence microscopy to visualise cells labelled with calcein AM and ethidium homodimer. RESULTS: Treatment with IL-1β (10 ng.ml(-1)) produced a large increase in sGAG release compared to untreated controls, but with no effect on cell viability, which was maintained above 80% for all treatments. In the absence of IL-1β, both n-3 compounds induced a mild catabolic response with increased loss of sGAG, particularly at 10 μM. By contrast, in the presence of IL-1β, both EPA and DHA at 0.1 and 1 μM significantly reduced IL-1β-mediated sGAG loss. The efficacy of the EPA treatment was maintained at approximately 75% throughout the 5-day period. However, at the same concentrations, the efficacy of DHA, although initially greater, reduced to approximately half that of EPA after 5 days. For both EPA and DHA, the highest dose of 10 μM was less effective. CONCLUSIONS: The results support the hypothesis that n-3 compounds are anti-inflammatory through competitive inhibition of the arachidonic acid oxidation pathway. The efficacy of these compounds is likely to be even greater at more physiological levels of IL-1β. Thus we suggest that n-3 PUFAs, particularly EPA, have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory joint disease.
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spelling pubmed-30465142011-03-01 Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation Wann, Angus KT Mistry, Jiten Blain, Emma J Michael-Titus, Adina T Knight, Martin M Arthritis Res Ther Research Article INTRODUCTION: In inflammatory joint disease, such as osteoarthritis (OA), there is an increased level of proinflammatory cytokines, such as interleukin (IL)-1β. These cytokines stimulate the production of matrix metalloproteinases (MMPs), which leads to the degradation of the cartilage extracellular matrix and the loss of key structural components such as sulphated glycosaminoglycan (sGAG) and collagen II. The aim of this study was to examine the therapeutic potential of n-3 polyunsaturated fatty acids (PUFAs) in an in vitro model of cartilage inflammation. METHODS: Two specific n-3 compounds were tested, namely, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), each at 0.1, 1 and 10 μM. Full thickness bovine cartilage explants, 5 mm in diameter, were cultured for 5 days with or without IL-1β and in the presence or absence of each n-3 compound. The media were replaced every 24 hours and assayed for sGAG content using the 1,9-dimethylmethylene blue (DMB) method. Chondrocyte viability was determined at the end of the culture period using fluorescence microscopy to visualise cells labelled with calcein AM and ethidium homodimer. RESULTS: Treatment with IL-1β (10 ng.ml(-1)) produced a large increase in sGAG release compared to untreated controls, but with no effect on cell viability, which was maintained above 80% for all treatments. In the absence of IL-1β, both n-3 compounds induced a mild catabolic response with increased loss of sGAG, particularly at 10 μM. By contrast, in the presence of IL-1β, both EPA and DHA at 0.1 and 1 μM significantly reduced IL-1β-mediated sGAG loss. The efficacy of the EPA treatment was maintained at approximately 75% throughout the 5-day period. However, at the same concentrations, the efficacy of DHA, although initially greater, reduced to approximately half that of EPA after 5 days. For both EPA and DHA, the highest dose of 10 μM was less effective. CONCLUSIONS: The results support the hypothesis that n-3 compounds are anti-inflammatory through competitive inhibition of the arachidonic acid oxidation pathway. The efficacy of these compounds is likely to be even greater at more physiological levels of IL-1β. Thus we suggest that n-3 PUFAs, particularly EPA, have exciting therapeutic potential for preventing cartilage degradation associated with chronic inflammatory joint disease. BioMed Central 2010 2010-11-08 /pmc/articles/PMC3046514/ /pubmed/21059244 http://dx.doi.org/10.1186/ar3183 Text en Copyright ©2010 Wann et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Wann, Angus KT
Mistry, Jiten
Blain, Emma J
Michael-Titus, Adina T
Knight, Martin M
Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
title Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
title_full Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
title_fullStr Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
title_full_unstemmed Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
title_short Eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
title_sort eicosapentaenoic acid and docosahexaenoic acid reduce interleukin-1β-mediated cartilage degradation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3046514/
https://www.ncbi.nlm.nih.gov/pubmed/21059244
http://dx.doi.org/10.1186/ar3183
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