Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF
Abstract 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-inflammat...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-06-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01150-z |
| _version_ | 1827922840649728000 |
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| author | Anais Defois Nina Bon Alexandre Charpentier Melina Georget Nicolas Gaigeard Frederic Blanchard Antoine Hamel Denis Waast Jean Armengaud Ophelie Renoult Claire Pecqueur Yves Maugars Marie-Astrid Boutet Jerome Guicheux Claire Vinatier |
| author_facet | Anais Defois Nina Bon Alexandre Charpentier Melina Georget Nicolas Gaigeard Frederic Blanchard Antoine Hamel Denis Waast Jean Armengaud Ophelie Renoult Claire Pecqueur Yves Maugars Marie-Astrid Boutet Jerome Guicheux Claire Vinatier |
| author_sort | Anais Defois |
| collection | DOAJ |
| description | Abstract 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. Video Abstract |
| first_indexed | 2024-03-13T04:48:31Z |
| format | Article |
| id | doaj.art-7a3c0f5b50e040b1ac7c119af7ea7643 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-13T04:48:31Z |
| publishDate | 2023-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-7a3c0f5b50e040b1ac7c119af7ea76432023-06-18T11:20:23ZengBMCCell Communication and Signaling1478-811X2023-06-0121111810.1186/s12964-023-01150-zOsteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNFAnais Defois0Nina Bon1Alexandre Charpentier2Melina Georget3Nicolas Gaigeard4Frederic Blanchard5Antoine Hamel6Denis Waast7Jean Armengaud8Ophelie Renoult9Claire Pecqueur10Yves Maugars11Marie-Astrid Boutet12Jerome Guicheux13Claire Vinatier14Nantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonDépartement Médicaments Et Technologies Pour La Santé (DMTS), Université Paris-Saclay, CEA, INRAE, SPINantes Université, INSERM, CNRSNantes Université, INSERM, CNRSNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonNantes Université, Oniris, CHU Nantes, INSERM, Regenerative Medicine and SkeletonAbstract 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. Video Abstracthttps://doi.org/10.1186/s12964-023-01150-zMetabolismInflammationOsteoarthritisChondrocytes |
| spellingShingle | Anais Defois Nina Bon Alexandre Charpentier Melina Georget Nicolas Gaigeard Frederic Blanchard Antoine Hamel Denis Waast Jean Armengaud Ophelie Renoult Claire Pecqueur Yves Maugars Marie-Astrid Boutet Jerome Guicheux Claire Vinatier Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF Cell Communication and Signaling Metabolism Inflammation Osteoarthritis Chondrocytes |
| 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 | Metabolism Inflammation Osteoarthritis Chondrocytes |
| url | https://doi.org/10.1186/s12964-023-01150-z |
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