Regulation of the phenotypic stability of chondrocytes by transmembrane heparan sulfate proteoglycans of the syndecan family

Basic data for this project

Description

Transmembrane heparan sulfate proteoglycans of the syndecan family have been proposed to bind a large variety of proteins and thereby mediate an array different functions in cells. Sdc-4 is of major importance during stress situtations like fracture healing, wound healing and in osteoarthritis (OA). In my prelimiary studies I have shown that Sdc-4 can be compensated by Sdc-2 during development, but not during diseases like OA and fracture healing. Furthermore, I have shown that Sdc-4 is involved in WNT signal transduction, which is important in both processes of embryogenesis and OA. Based on my preliminary data I therefore hypothezise that Sdc-2 and -4 play a vital role in regulating chondrocyte phenotype and differentiation. In my project, I want to focus on the mechanisms of WNT induced signal transduction via syndecans, particularly Sdc-2 and-4. Furthermore, I want to use in both in vitro analyses with isolated chondrocytes and in vivo studies using wild type and syndecan- deficient animals to investigate the role of WNT signalling pathways in regulating the phenotypic stability of chondrocytes and their function in OA.. The results of this grant will lead to a better understanding of pathogenic mechanisms of OA and help to pave the path to new therapeutic approaches for this disease.