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
Laboratory of Rheumatology, GIGA Research, CHU de Liège, University of Liège, 4000 Liège, Belgium.
Orthopedic Surgery Department, CHU de Liège, 4000 Liège, Belgium.
J Clin Med. 2021 Nov 16;10(22):5331. 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).
Cellular senescence was assessed via the proliferation rate, β-galactosidase staining, DNA damage and CKI expression (p21, p16). Experimental senescence was induced by irradiation.
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. 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.
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.
骨关节炎（OA）被认为是一种与细胞衰老相关的疾病。糖皮质激素（GC）关节内注射常用于膝骨关节炎以治疗滑膜积液，但在毒性方面存在争议。我们研究了GC对骨关节炎患者成纤维样滑膜细胞（FLS）和间充质干细胞（MSC）的细胞衰老特征及衰老诱导的影响。
通过增殖率、β-半乳糖苷酶染色、DNA损伤和CKI表达（p21、p16）评估细胞衰老。通过辐射诱导实验性衰老。
GC泼尼松龙在FLS中未诱导明显的衰老表型，增殖甚至更高，β-半乳糖苷酶阳性细胞无积累，无DNA损伤，p21mRNA减少，仅显示p16增强。泼尼松龙未改变FLS中的实验性衰老诱导，对任何衰老参数均无调节作用。此外，泼尼松龙在MSC中未诱导衰老表型：尽管β-半乳糖苷酶阳性细胞较多，但未观察到增殖减少、DNA损伤和CKI增强。
我们提供了关于GC在骨关节炎细胞衰老方面应用的令人放心的体外数据：GC泼尼松龙在骨关节炎FLS（增殖率甚至更高）和MSC中未诱导衰老表型，也未使细胞衰老加剧。
