Scientists of Biomedcode present in PLOS Computational Biology a new computational framework revealing key differences between four rheumatoid arthritis medications and their impact on biological pathways in mice.
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.
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.
Characterization and non-clinical assessment of the proposed etanercept biosimilar GP2015 with originator etanercept (Enbrel®). Hans-Peter Hofmann, Ulrich Kronthaler, Cornelius Fritsch, Roger Grau, Stefan O. Müller, Robert Mayer, Andreas Seidl, and Antonio Da Silva. Expert Opinion on Biological Therapy Vol. 16 , Iss. 10, 2016
Biomedcode’s human TNF transgenic arthritis model, (Tg197), contributes to the non-clinical assessment of etanercept biosimilar GP2015 with originator etanercept (Enbrel).
Michopoulos F, Karagianni N, Whalley NM, Firth MA, Nikolaou C, Wilson ID, Critchlow SE, Kollias G, Theodoridis GA. Targeted metabolic profiling of the Tg197 mouse model reveals itaconic acid as a marker of Rheumatoid Arthritis. J Proteome Res. 15: 4579-90 (2016 ).
Biomedcode coauthors a publication in the Journal of Proteome Research on the identification of a biomarker with translational value for the diagnosis and monitoring of rheumatoid arthritis disease and therapy.