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Sox9 and adult bone marrow derived mesenchymal stem cells (MSC)

Sox9 和成人骨髓来源的间充质干细胞 (MSC)

基本信息

批准号：
34609612
负责人：
Professorin Dr. Susanne Grässel
金额：
--
依托单位：
Abteilung Experimentelle Orthopädie
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2007
资助国家：
德国
起止时间：
2006-12-31 至 2012-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/34609612?language=en
关键词：
Sox9 adult bone marrow derived

项目摘要

Cell-fate determination of pluripotent cells, cell proliferation, differentiation, maturation and maintenance of stem cells are essential cellular events during longitudinal skeletal growth. Master transcription factor Sox9 is required for formation of both permanent and replacement cartilage. During embryogenesis Sox9 is expressed in all osteochondroprogenitor cells and chondrocytes, where, among other functions, it is required for mesenchymal condensation and inhibition of precocious hypertrophic conversion of proliferating chondrocytes. We have inhibited Sox9 in vitro in adult bone marrow derived mesenchymal stem cells (MSC) by RNAi interference (RNAi). The aim of our study is to determine the role of Sox9 in adult MSC and its impact on osteochondrogenic differentiation capacity and cell survival. (1) We want to delineate the role of Sox9 in controlling proliferation and vitality of MSC. (2) We want to delineate the underlying signal transduction pathway mediating Sox9 effects on cell survival. (3) We want to determine osteo-chondrogenic differentiation capacity of Sox9 inhibited MSC with particular respect to hypertrophic conversion and osteogenesis. No pharmacological approach to the regulation of Sox9 expression and function in MSC has been reported as to now. Thus, unraveling the consequences of Sox9 regulation in multipotent MSC might help to develop concepts for treatment of chondral lesions and degenerative joint and disc diseases.

多能细胞的命运决定、细胞增殖、分化、成熟和干细胞的维持是纵向骨骼生长过程中必不可少的细胞事件。永久软骨和替代软骨的形成都需要主转录因子Sox9。在胚胎发生过程中，Sox9在所有骨软骨祖细胞和软骨细胞中表达，其中除其他功能外，还需要间充质凝聚和抑制增殖软骨细胞的早熟肥厚转化。我们通过RNAi干扰（RNAi）在体外抑制成人骨髓间充质干细胞（MSC）中的Sox9。我们的研究目的是确定Sox9在成人间充质干细胞中的作用及其对骨软骨分化能力和细胞存活的影响。(1)我们想要描述Sox9在控制MSC增殖和活力中的作用。(2)我们想要描述介导Sox9对细胞存活影响的潜在信号转导途径。(3)我们想要确定Sox9抑制MSC的骨-软骨分化能力，特别是在肥厚转化和成骨方面。到目前为止，还没有关于Sox9在MSC中表达和功能调控的药理学方法报道。因此，揭示多能间充质干细胞中Sox9调控的结果可能有助于开发软骨病变和退行性关节和椎间盘疾病的治疗概念。