软骨终板干细胞通过BMP-2介导的Smad依赖性信号通路调节髓核细胞增殖

项目名称： 软骨终板干细胞通过BMP-2介导的Smad依赖性信号通路调节髓核细胞增殖

项目编号： No.81472131

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 王建

作者单位： 中国人民解放军第三军医大学

项目金额： 72万元

中文摘要： 软骨终板退变可能是髓核退变的始动因素，软骨终板钙化使营养交换减少，造成髓核进一步退变，但是有关软骨终板导致髓核早期退变的机制不清。本课题组在前期研究中发现人退变软骨终板中存在干细胞并命名为CESCs，并在该细胞和NPCs中证实存在骨形成蛋白-2（BMP-2）及Smad依赖性信号通路相关分子（Smad1/5/8）。为此，我们假设BMP-2是NPCs增殖的调节因子，CESCs以旁分泌BMP-2方式，通过Smad依赖性信号通路，调控NPCs增殖，影响椎间盘退变。本研究建立CESCs和NPCs共培养体系，采用BMP-2基因沉默和腺病毒转染方法，BMP-2腺病毒载体保护退变椎间盘动物实验，观测BMP-2介导Smad依赖性通路信号分子表达，探讨CESCs对NPCs增殖的调节作用。本研究将证实CESCs通过BMP-2介导的Smad依赖性信号通路调控NPCs增殖，为椎间盘退变治疗提供新的思路。

中文关键词： 椎间盘退变；干细胞；软骨细胞；髓核细胞；信号通路

英文摘要： Disc degeneration is related with the death of nuclues pulposus cells (NPCs) caused by stress and nutritional change. Recent studies has proven that cartilage endplate degeneration may be initiating factor of nucleus pulposus degeneration. Calificed cartilage endplate lead to decreased nutritional exchange and further nucleus pulposus degeneration.To our knowledge, the molecular mechanism for early nucleus pulposus degeneration caused by cartilage endplate has not been clarified. In our previous work, we conclusively indicated the presence of progenitor cells in degenerated cartilage endplate, and gave those cells the name as CESCs. Bone morphogenetic protein 2 (BMP-2) and signalling molecules related to Smad dependent signal pathway such as Smad 1/5/8 and receptors of BMP-2 were respectively found in CESCs and NPCs. Therefore, we make the hypothesis that BMP-2 is a regulating factor of NPCs proliferation. CESCs regulate NPCs proliferation and play a role in disc degeneration via paracrine BMP-2 and Smad dependent signal pathway.In this study, we shall set up coculture system of CESCs and NPCs, and make use of BMP-2siRNA and recombinant adenoviral vector carrying the human BMP-2 gene.The expression of signalling molecule of Smad dependent pathway mediated by BMP-2 will be observed. The purpose of this study is to confirm that CESCs regulate NPCs proliferation by means of BMP-2 mediated Smad dependent signal pathway, and to provide a novel rationale for disc degeneration therapy.

英文关键词： disc degeneration;stem cell;chondrocyte;nucleus pulposus cell;signal pathway