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

• Published in: Journal of clinical medicine Vol. 10; no. 22; p. 5331
• Main Authors: Malaise, Olivier, Paulissen, Geneviève, Deroyer, Céline, Ciregia, Federica, Poulet, Christophe, Neuville, Sophie, Plener, Zelda, Daniel, Christophe, Gillet, Philippe, Lechanteur, Chantal, Brondello, Jean-Marc, de Seny, Dominique, Malaise, Michel
• Format: Journal Article Web Resource
• Language: English
• Published: Basel MDPI AG 16.11.2021; MDPI
• Subjects: Antibodies; Biopsy; Bone surgery; Cartilage; Cell cycle; Cell growth; Clinical medicine; Cyclin-dependent kinases; Experiments; Fibroblasts; Gene expression; Histology; Human health sciences; Kinases; Manufacturers; Rheumatology; Rhumatologie; Sciences de la santé humaine; Senescence; Belgium; United States > US; Germany
• ISSN: 2077-0383; 2077-0383
• DOI: 10.3390/jcm10225331

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, p16INK4A). 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 p16INK4A. 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.