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Targeting senescence and inflammation in chronic destructive TNF-driven joint pathology. | LitMetric

Targeting senescence and inflammation in chronic destructive TNF-driven joint pathology.

Mech Ageing Dev

First Department of Propaedeutic Internal Medicine and Joint Academic Rheumatology Program, National and Kapodistrian University of Athens Medical School, 11527 Athens, Greece; Center for New Biotechnologies and Precision Medicine, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Postgraduate Medical Studies in Geriatric Syndromes and Physiology of Aging, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Published: September 2023

AI Article Synopsis

Article Abstract

We had shown 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, we 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.

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Source
http://dx.doi.org/10.1016/j.mad.2023.111856DOI Listing

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