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

Defois, Anais;Bon, Nina;Charpentier, Alexandre;Georget, Melina;Vinatier, Claire;et.al.
(2023) Cell Communication and Signaling — Vol. 21, n° 1 (2023) (2023)

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Authors
  • Defois, Anais
    Author
  • Bon, Nina
    Author
  • Charpentier, Alexandre
    Author
  • Georget, Melina
    Author
  • Author
  • Vinatier, Claire
    Author
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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.
Affiliations
  • Université de NantesCentre de Recherche en Cancérologie et Immunologie Nantes-Angers UMR1232, INSERM

Citations

Defois, A., Bon, N., Charpentier, A., Georget, M., Gaigeard, N., Blanchard, F., Hamel, A., Waast, D., Armengaud, J., Renoult, O., Pecqueur, C., Maugars, Y., Boutet, M.-A., Guicheux, J., & Vinatier, C. (2023). Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF. Cell Communication and Signaling, 21(1 (2023)). https://doi.org/10.1186/s12964-023-01150-z (Original work published 2023)