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

Abstract

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.

The protective effects of Phoenixin-20 in tumor necrosis factor α (TNF-α)-induced cell senescence of rheumatoid arthritis fibroblast-like synoviocytes (FLS)

“…Inhibition of proliferation and induction of apoptosis of RA FLS may be a feasible ideal strategy for RA treatment [ 12 ]. Recent studies have shown that the cell senescence of FLS is involved in the pathological process of arthritis [ 13 , 14 ]. Furthermore, the senescence induced by chronic inflammation is found to participate in the progression of RA by impairing the immunomodulatory properties of synovial fluid mesenchymal stem cells [ 15 ].…”

Strontium ion attenuates osteoarthritis through inhibiting senescence and enhancing autophagy in fibroblast-like synoviocytes

“…Among them, synovial in ammation is a serious risk factor [9]. With the increase of age, broblast-like synoviocytes (FLSs) show senescence and exhibit a senescence-associated secretory phenotype (SASP) [10][11][12]. Senescent FLSs highly express in ammatory cytokines such as IL-1 and IL-6 [12], leading to high in ammatory responses in the articular cavity.…”

“…With the increase of age, broblast-like synoviocytes (FLSs) show senescence and exhibit a senescence-associated secretory phenotype (SASP) [10][11][12]. Senescent FLSs highly express in ammatory cytokines such as IL-1 and IL-6 [12], leading to high in ammatory responses in the articular cavity. Senescent FLSs can also secrete matrix metalloproteases (MMPs), resulting in cartilage destruction [13,14].…”