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

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

doi:10.3390/jcm10225331

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

J Clin Med. 2021 Nov 16;10(22):5331. doi: 10.3390/jcm10225331.

Affiliations

¹ Laboratory of Rheumatology, GIGA Research, CHU de Liège, University of Liège, 4000 Liège, Belgium.
² Orthopedic Surgery Department, CHU de Liège, 4000 Liège, Belgium.
³ Laboratory of Cell and Gene Therapy, Department of Hematology, CHU de Liège, 4000 Liège, Belgium.
⁴ Institute for Regenerative Medicine and Biotherapy, Univ Montpellier, INSERM UMR1183, 34298 Montpellier, France.

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, p16^INK4A). 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^INK4A. 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.

Keywords: clinical studies; osteoarthritis; synovial membrane.