GLUCOSE DEPLETION DECREASES CELL VIABILITY WITHOUT TRIGGERING DEGENERATIVE CHANGES IN A PHYSIOLOGICAL NUCLEUS PULPOSUS EXPLANT MODEL - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Journal of Orthopaedic Research Année : 2023

GLUCOSE DEPLETION DECREASES CELL VIABILITY WITHOUT TRIGGERING DEGENERATIVE CHANGES IN A PHYSIOLOGICAL NUCLEUS PULPOSUS EXPLANT MODEL

Résumé

Although the etiology of intervertebral disc degeneration is still unresolved, the nutrient paucity resulting from its avascular nature is suspected of triggering degenerative processes in its core: the nucleus pulposus (NP). While severe hypoxia has no significant effects on NP cells, the impact of glucose depletion, such as found in degenerated discs (0.2-1 mM), is still uncertain. Using a pertinent ex vivo model representative of the unique disc microenvironment, the present study aimed, therefore, at determining the effects of "degenerated" (0.3 mM) glucose levels on bovine NP explant homeostasis. The effects of glucose depletion were evaluated on NP cell viability, apoptosis, phenotype, metabolism, senescence, extracellular matrix anabolism and catabolism, and inflammatory mediator production using fluorescent staining, RT-qPCR, (immuno)histology, ELISA, biochemical, and enzymatic assays. Compared to the "healthy" (2 mM) glucose condition, exposure to the degenerated glucose condition led to a rapid and extensive decrease in NP cell viability associated with increased apoptosis. Although the aggrecan and collagen-II gene expression was also downregulated, NP cell phenotype, and senescence, matrix catabolism, and inflammatory mediator production were not, or only slightly, affected by glucose depletion. The present study provided evidence for glucose depletion as an essential player in NP cell viability but also suggested that other micro-environment factor(s) may be involved in triggering the typical shift of NP cell phenotype observed during disc degeneration. The present study contributes new information for better understanding disc degeneration at the cellular-molecular levels and thus helps to develop relevant therapeutical strategies to counteract it.
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Dates et versions

hal-04321390 , version 1 (04-12-2023)

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Mathilde Padrona, Manon Maroquenne, Hanane El-Hafci, Lucille Rossiaud, Hervé Petite, et al.. GLUCOSE DEPLETION DECREASES CELL VIABILITY WITHOUT TRIGGERING DEGENERATIVE CHANGES IN A PHYSIOLOGICAL NUCLEUS PULPOSUS EXPLANT MODEL. Journal of Orthopaedic Research, In press, ⟨10.1002/jor.25742⟩. ⟨hal-04321390⟩
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