Targeting Senescence and Inflammation in Chronic Destructive TNF-driven Joint Pathology

This study showed that administration of the senolytic Dasatinib abolishes arthritis in the human TNF transgenic mouse model of chronic destructive arthritis when given in combination with a sub-therapeutic dose of the anti-TNF mAb Infliximab (1 mg/kg). Herein, it was found that while the number of senescent chondrocytes (GL13+/Ki67-), assessed according to guideline algorithmic approaches, was not affected by either Dasatinib or sub-therapeutic Infliximab monotherapies, their combination reduced senescent chondrocytes by 50 %, which was comparable to levels observed with therapeutic Infliximab monotherapy (10 mg/kg). This combination therapy also reduced the expression of multiple factors of senescence-associated secretory phenotype in arthritic joints.
Studies to elucidate the interplay of inflammation and senescence may help in optimizing treatment strategies also for age-related pathologies characterized by chronic low-grade joint inflammation.

Original publication:

Nikolaos I. Vlachogiannis, Konstantinos Evangelou, Lydia Ntari, Christoforos Nikolaou, Maria C. Denis, Niki Karagianni, Dimitris Veroutis, Vassilis Gorgoulis, George Kollias and Petros P. Sfikakis., Targeting Senescence and Inflammation in Chronic Destructive TNF-driven Joint Pathology, Mechanisms of Ageing and Development, Volume 214, September 2023, 111856. doi: 10.1016/j.mad.2023.111856