Senescent synovial fibroblasts accumulate prematurely in rheumatoid arthritis tissues and display an enhanced inflammatory phenotype

• DOI: 10.1186/s12979-019-0169-4
• Publication Date: 2019-11-05T15:17:19Z
• Authors: Manuel J. Del Rey; Álvaro Valín; Alicia Usategui; Sandra Ergueta; Eduardo Martín; Cristina Municio; Juan D. Cañete; Francisco J. Blanco; Gabriel Criado; José L. Pablos
• Keywords: Senescence; MMP3; Interleukin 8

Abstract Background Accumulation of senescent cells has been associated with pro-inflammatory effects deleterious consequences in different human diseases. The purpose this study was to analyze cell senescence synovial tissues (ST), and its impact on the function fibroblasts (SF). Results expression marker p16INK4a (p16) analyzed by immunohistochemistry rheumatoid arthritis (RA), osteoarthritis (OA), normal ST from variably aged donors. proportion p16(+) older donors higher than younger ones. Although RA OA showed proportions similar ST, increased compared age-matched ST. percentage SA-β-gal(+) SF after 14 days culture positively correlated donor’s age. Initial exposure H 2 O or TNFα enhanced mRNA IL6 , CXCL8 CCL2 MMP3 proteins secretion. Senescent show a heightened IL-6 IL-8 protein response upon further challenge TNFα. Treatment senolytic drug fenofibrate normalized expression. Conclusions increases aging prematurely patients. Senescence cultured is accelerated oxidative stress may contribute pathogenesis synovitis increasing production mediators.