Project Details
Projekt
Matrix mediated fibroblast activation in rheumatoid arthritis
Applicants
Dr. Adelheid Korb-Pap; Professor Dr. Thomas Pap
Subject Area
Orthopaedics, Traumatology, Reconstructive Surgery
Term
since 2018
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 384170921
Rheumatoid arthritis (RA) is a chronic autoimmune disease that primarily affects the joints and that leads to their progressive destruction. Apart form inflammatory cells, mesenchymal cells of the synovial membrane, the fibroblast-like synoviocytes (FLSs) play a central role in the pathogenesis of RA by transforming into invasively growing, tumour-like cells. Although the exact causes and mechanisms of this transformation still remain unclear, several lines of evidence indicate that the interaction of RA-FLSs with the articular cartilage and components of its extracellular matrix (ECM) are of central importance. Previously, we have shown that cell surface receptors, particularly integrins, mediate the interaction of RA-FLSs with the cartilage ECM and lead to the development of so-called invadopodia, invasive cellular structures that contribute to FLS-mediated cartilage destruction. Further, we showed that the development of invadopodia in RA-FLSs is associated with the increased expression of adaptor molecules that regulate the organization of the cytoskeleton. In this project, we aim to identify the ECM components that lead to the stimulation of FLSs in RA and to elucidate the underlying molecular mechanisms. Based on these findings, we aim to develop novel therapeutic principles for RA that target the ECM-mediated transformation of RA-FLSs and, thus, go beyond currently used, largely anti-inflammatory therapeutic approaches
DFG Programme
Research Units
