Development of DNA Damage-Induced Senescence Model in Osteoarthritic Chondrocytes | Aging-US



September 19, 2023

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  • Aging-US published this trending research paper on September 1, 2023, in Volume 15, Issue 17, entitled, “Development of a DNA damage-induced senescence model in osteoarthritic chondrocytes" by researchers from Nantes Université, Oniris, CHU Nantes, Inserm, Regenerative Medicine and Skeleton RMeS, UMR 1229, Nantes F-44000, France. DOI - Corresponding author - Claire Vinatier - Abstract Senescent cells (SnCs) have been described to accumulate in osteoarthritis (OA) joint tissues in response to injury, thereby participating in OA development and progression. However, clinical therapeutic approaches targeting SnCs using senolysis, although promising in preclinical OA models, have not yet proven their efficacy in patients with knee OA. This pitfall may be due to the lack of understanding of the mechanisms underlying chondrocyte 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 entail inflammation-related senescence in human OA chondrocytes. Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. Chronic exposure to IL-1β induces only partial expression of senescence markers and does not allow us to conclude on its ability to induce senescence in chondrocytes. On the other hand, etoposide treatment reliably induces DNA damage-related senescence in human articular chondrocytes evidenced by loss of proliferative capacity, 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. Sign up for free Altmetric alerts about this article - Subscribe for free publication alerts from Aging - Keywords - aging, senescence, osteoarthritis, etoposide, chondrocytes About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at​​ and connect with us: SoundCloud - Facebook - X - Instagram - YouTube - LinkedIn - Pinterest - Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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