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

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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.