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

多聚糖家族跨膜硫酸乙酰肝素蛋白聚糖对软骨细胞表型稳定性的调节

基本信息

批准号：
222638836
负责人：
Professorin Dr. Jessica Bertrand
金额：
--
依托单位：
Orthopädische Universitätsklinik
依托单位国家：
德国
项目类别：
Independent Junior Research Groups
财政年份：
2013
资助国家：
德国
起止时间：
2012-12-31 至 2018-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/222638836?language=en
关键词：
Regulation phenotypic stability chondrocytes transmembrane

项目摘要

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.

已经提出多配体蛋白聚糖家族的跨膜硫酸乙酰肝素蛋白聚糖结合多种蛋白质，从而介导细胞中的一系列不同功能。Sdc-4在骨折愈合、伤口愈合和骨关节炎（OA）等应激情况下非常重要。在我的前期研究中，我已经表明，Sdc-4可以在发育过程中被Sdc-2补偿，但在OA和骨折愈合等疾病中不能。此外，我已经表明，Sdc-4参与WNT信号转导，这是重要的胚胎发育和OA的过程。基于我的初步数据，我因此假设Sdc-2和-4在调节软骨细胞表型和分化中起着至关重要的作用。在我的项目中，我想专注于WNT通过syndecans诱导的信号转导机制，特别是Sdc-2和-4。此外，我想在使用分离的软骨细胞的体外分析和使用野生型和syndecan缺陷动物的体内研究中使用，以研究WNT信号传导途径在调节软骨细胞的表型稳定性及其在OA中的功能中的作用。这项资助的结果将有助于更好地了解OA的致病机制，并有助于为这种疾病的新治疗方法铺平道路。