利用EP1敲除小鼠模型研究调节间充质干细胞生长和分化的关键基因

项目名称： 利用EP1敲除小鼠模型研究调节间充质干细胞生长和分化的关键基因

项目编号： No.81200255

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 张玟洁

作者单位： 中国科学院深圳先进技术研究院

项目金额： 23万元

中文摘要： 除了作为血液干细胞巢的重要成员，间充质干细胞还承担着调节骨再生的重要功能。然而间充质干细胞生长和分化的调节机理仍不清楚。前期的研究已经证实了：1）EP1敲除小鼠中间充质干细胞生长和分化加速；2）PTH间断注射也会刺激间质干细胞分化。因此，同时被EP1通过钙信号传导以及PTH通过PKA信号传导所共同调控的基因很可能具有重要的调节间质干细胞的功能。为了揭示间充质干细胞的调节机理，采取的科研手段有：1）用微阵列技术以及RT-PCR技术筛选被EP1及PTH共同调控其RNA表达的目标基因；2）用体外细胞分化实验验证筛选的目标基因是否具有调节间充质干细胞的能力；3）用小鼠皮质骨骨折模型以及骨嫁接模型进一步验证目标基因调解间充质干细胞的能力,通过调节间充质干细胞达到促进骨生长的作用。间充质干细胞调节基因的确定以及调节对研究衰老过程中出现的间充质干细胞缺陷具有重要的作用。

中文关键词： PGE2；EP1；骨质疏松；骨折愈合；间充质细胞

英文摘要： Mesenchymal stem cell (MSC), in addition to be a crucial component of the hematopoietic stem cell niche, has been confirmed to be responsible to bone regeneration. However, the underlying mechanism of MSC proliferation and differentiation has not been clarified. Previous studies well confirmed that 1) EP1-/- mice exhibit increased MSC population and accelerated differentiation into osteoblasts; 2) PTH intermittent treatment stimulates MSC differentiation. Therefore, genes regulated by both EP1, via calcium signaling, and PTH, via PKA signaling, may play important role in regulating MSC functions. The current proposal attempts to elucidate the mechanism of mesenchymal stem cell regulation by i) screening genes that regulated by both EP1 and PTH signaling by micro-array assay and RT-PCR; ii) using in vitro differentiation assay to confirm that EP1/PTH signaling target genes are able to regulate MSC funstion; iii) using cortical bone defect model and murine graft model to confirm target genes in vivo and to promote bone formation by controlling MSC differentiation. Identifying the genes that involved in regulating MSC function and controling their expression level will significantly contribute to the study in aging induced MSC defects.

英文关键词： PGE2；EP1；Osteoporosis；Fracture Healing；Mesenchymal Stem Cell