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Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF

BACKGROUND: Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cyto...

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Autores principales: Defois, Anais, Bon, Nina, Charpentier, Alexandre, Georget, Melina, Gaigeard, Nicolas, Blanchard, Frederic, Hamel, Antoine, Waast, Denis, Armengaud, Jean, Renoult, Ophelie, Pecqueur, Claire, Maugars, Yves, Boutet, Marie-Astrid, Guicheux, Jerome, Vinatier, Claire
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265918/
https://www.ncbi.nlm.nih.gov/pubmed/37316888
http://dx.doi.org/10.1186/s12964-023-01150-z
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author Defois, Anais
Bon, Nina
Charpentier, Alexandre
Georget, Melina
Gaigeard, Nicolas
Blanchard, Frederic
Hamel, Antoine
Waast, Denis
Armengaud, Jean
Renoult, Ophelie
Pecqueur, Claire
Maugars, Yves
Boutet, Marie-Astrid
Guicheux, Jerome
Vinatier, Claire
author_facet Defois, Anais
Bon, Nina
Charpentier, Alexandre
Georget, Melina
Gaigeard, Nicolas
Blanchard, Frederic
Hamel, Antoine
Waast, Denis
Armengaud, Jean
Renoult, Ophelie
Pecqueur, Claire
Maugars, Yves
Boutet, Marie-Astrid
Guicheux, Jerome
Vinatier, Claire
author_sort Defois, Anais
collection PubMed
description BACKGROUND: Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. METHODS: Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays. RESULTS: We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF. CONCLUSION: These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01150-z.
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spelling pubmed-102659182023-06-15 Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF Defois, Anais Bon, Nina Charpentier, Alexandre Georget, Melina Gaigeard, Nicolas Blanchard, Frederic Hamel, Antoine Waast, Denis Armengaud, Jean Renoult, Ophelie Pecqueur, Claire Maugars, Yves Boutet, Marie-Astrid Guicheux, Jerome Vinatier, Claire Cell Commun Signal Research BACKGROUND: Osteoarthritis is an age-related disease that currently faces a lack of symptomatic treatment. Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1b, TNF, and IL-6, plays an important role in osteoarthritis progression. In this context, pro-inflammatory cytokines are widely used to mimic the inflammatory component of osteoarthritis in vitro. However, the therapeutic failures of clinical trials evaluating anti-cytokines drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. METHODS: Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. Then, the dysregulations highlighted at the molecular level were functionally confirmed by real-time cellular metabolic assays. RESULTS: We identified dysregulation of metabolic-related genes in osteoarthritic chondrocytes but not in non-osteoarthritic chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically confirmed in osteoarthritic chondrocytes treated with IL-1b or TNF. CONCLUSION: These data show a strong and specific association between inflammation and metabolism in osteoarthritic chondrocytes, which was not found in non-osteoarthritic chondrocytes. This indicates that the link between inflammation and metabolic dysregulation may be exacerbated during chondrocyte damage in osteoarthritis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12964-023-01150-z. BioMed Central 2023-06-14 /pmc/articles/PMC10265918/ /pubmed/37316888 http://dx.doi.org/10.1186/s12964-023-01150-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Defois, Anais
Bon, Nina
Charpentier, Alexandre
Georget, Melina
Gaigeard, Nicolas
Blanchard, Frederic
Hamel, Antoine
Waast, Denis
Armengaud, Jean
Renoult, Ophelie
Pecqueur, Claire
Maugars, Yves
Boutet, Marie-Astrid
Guicheux, Jerome
Vinatier, Claire
Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
title Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
title_full Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
title_fullStr Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
title_full_unstemmed Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
title_short Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
title_sort osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to il-1b or tnf
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10265918/
https://www.ncbi.nlm.nih.gov/pubmed/37316888
http://dx.doi.org/10.1186/s12964-023-01150-z
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