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Development of a DNA damage-induced senescence model in osteoarthritic chondrocytes
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Edité par CCSD ; Impact Journals -
International audience. Senescent cells (SnCs) have been described to accumulate in osteoarthritis (OA) joint tissues in response toinjury, thereby participating in OA development and progression. However, clinical therapeutic approachestargeting SnCs using senolysis, although promising in preclinical OA models, have not yet proven their efficacyin patients with knee OA. This pitfall may be due to the lack of understanding of the mechanisms underlyingchondrocyte senescence. Therefore, our study aimed to generate models of chondrocyte senescence.This study used etoposide, to induce DNA damage-related senescence or chronic exposure to IL-1β to entailinflammation-related senescence in human OA chondrocytes. Several hallmarks of cellular senescence, such ascell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associatedsecretory profile were evaluated.Chronic exposure to IL-1β induces only partial expression of senescence markers and does not allow us toconclude on its ability to induce senescence in chondrocytes. On the other hand, etoposide treatment reliablyinduces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferativecapacity, DNA damage accumulation, and expression of some SASP components.Etoposide-induced senescence model may help investigate the initiation of cellular senescence in chondrocytes,and provide a useful model to develop therapeutic approaches to target senescence in OA.
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