Influence of Glucocorticoids on Cellular Senescence Hallmarks in Osteoarthritic Fibroblast-like Synoviocytes

Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks an...

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Autores principales: Olivier Malaise, Geneviève Paulissen, Céline Deroyer, Federica Ciregia, Christophe Poulet, Sophie Neuville, Zelda Plener, Christophe Daniel, Philippe Gillet, Chantal Lechanteur, Jean-Marc Brondello, Dominique de Seny, Michel Malaise
Formato: article
Lenguaje:EN
Publicado: MDPI AG 2021
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R
Acceso en línea:https://doaj.org/article/34cc2a99573a4e5a867fd07d7f611b83
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Sumario:Osteoarthritis (OA) is recognized as being a cellular senescence-linked disease. Intra-articular injections of glucocorticoids (GC) are frequently used in knee OA to treat synovial effusion but face controversies about toxicity. We investigated the influence of GC on cellular senescence hallmarks and senescence induction in fibroblast-like synoviocytes (FLS) from OA patients and mesenchymal stem cells (MSC). Methods: Cellular senescence was assessed via the proliferation rate, β-galactosidase staining, DNA damage and CKI expression (p21, p16<sup>INK4A</sup>). Experimental senescence was induced by irradiation. Results: The GC prednisolone did not induce an apparent senescence phenotype in FLS, with even higher proliferation, no accumulation of β-galactosidase-positive cells nor DNA damage and reduction in p21mRNA, only showing the enhancement of p16<sup>INK4A</sup>. Prednisolone did not modify experimental senescence induction in FLS, with no modulation of any senescence parameters. Moreover, prednisolone did not induce a senescence phenotype in MSC: despite high β-galactosidase-positive cells, no reduction in proliferation, no DNA damage and no CKI enhancement was observed. Conclusions: We provide reassuring in vitro data about the use of GC regarding cellular senescence involvement in OA: the GC prednisolone did not induce a senescent phenotype in OA FLS (the proliferation ratio was even higher) and in MSC and did not worsen cellular senescence establishment.