Patients with rheumatoid arthritis and spondyloarthritis show higher mortality rates, mainly caused by cardiac comorbidities. The TghuTNF (Tg197) arthritis model develops tumour necrosis factor (TNF)-driven and mesenchymal synovial fibroblast (SF)-dependent polyarthritis. Here, we investigate whether this model develops, similarly to human patients, comorbid heart pathology and explore cellular and molecular mechanisms linking arthritis to cardiac comorbidities.
Biomedcode scientists coauthor two publications, one in Annals of Rheumatic diseases and one in JCI insight, showing that Tg197 and TNFΔΑRΕ mice develop heart valve pathology sharing common mesenchymal cell-specific aetiopathogenic mechanisms with arthritis.
Mesenchymal TNF signaling is etiopathogenic for inflammatory diseases such as rheumatoid arthritis and spondyloarthritis (SpA). The role of Tnfr1 in arthritis has been documented; however, Tnfr2 functions are unknown. Here, we investigate the mesenchymal-specific role of Tnfr2 in the TnfΔARE mouse model of SpA in arthritis and heart valve stenosis comorbidity by cell-specific, Col6a1-cre-driven gene targeting. We find that TNF/Tnfr2 signaling in resident synovial fibroblasts (SFs) and valvular interstitial cells (VICs) is detrimental for both pathologies, pointing to common cellular mechanisms. In contrast, systemic Tnfr2 provides protective signaling, since its complete deletion leads to severe deterioration of both pathologies. SFs and VICs lacking Tnfr2 fail to acquire pathogenic activated phenotypes and display increased expression of antiinflammatory cytokines associated with decreased Akt signaling.
Biomedcode’s human TNF transgenic arthritis model, (Tg197), contributes to the non-clinical assessment of adalimumab biosimilar GP2017 with originator Humira.
Biomedcode is pleased to announce that it has received national funding from the General Secretary for Research and Technology supporting the innovative research networks HUPLA and BreasCaRANKL that combine the efforts of industrial and renowned academic partners to develop precision drug evaluation tools for the preclinical development of novel therapies for Multiple Sclerosis and Breast Cancer.