颌骨骨巨细胞瘤中Fas/FasL介导间充质干细胞诱导CD14+巨噬细胞凋亡的机制研究

项目名称： 颌骨骨巨细胞瘤中Fas/FasL介导间充质干细胞诱导CD14+巨噬细胞凋亡的机制研究

项目编号： No.31501121

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 生物科学

项目作者： 董智伟

作者单位： 中国人民解放军北部战区总医院

项目金额： 20万元

中文摘要： 近年来研究发现Fas/FasL信号通路能够介导破骨细胞凋亡，本课题组在前期研究中发现，颌骨骨巨细胞瘤来源MSCs（GMSCs）的FasL表达下降且GMSCs体外诱导CD14+巨噬细胞凋亡减少，巨噬细胞作为破骨细胞的前体细胞影响破骨细胞生成，据此我们提出GMSCs通过Fas/FasL途径诱导CD14+巨噬细胞凋亡减少导致颌骨骨巨细胞瘤中破骨细胞增多的假说。本课题拟以正常颌骨来源MSCs（JBMSCs）为对照，分别从GMSCs诱导CD14+巨噬细胞凋亡情况，Fas/FasL介导GMSCs诱导的CD14+单核/巨噬细胞凋亡及其分子机制，动物模型验证等方面探讨Fas/FasL在MSCs调控破骨细胞凋亡及其在颌骨骨巨细胞瘤发病中的作用及分子机制。本课题不但能够明确MSCs参与颌骨骨巨细胞瘤骨破坏的新机理，而且提出以Fas/FasL为靶点治疗骨巨细胞瘤，具有重要的理论和临床意义。

中文关键词： 细胞凋亡；间充质干细胞；干细胞分化

英文摘要： Recent study showed that apoptosis of osteoclast can be regulated via Fas/FasL pathway. Our previous work found that the expression of FasL decreased in MSCs derived from giant cell tumor of jaw (GMSCs). And GMSCs reduced the apoptosis of CD14+ macrophage in vitro. In addition, macrophage could regulate generation of osteoclast as pre-osteoclast. Based on these results, we hypothesize that apoptosis reduction of CD14+ macrophage by GMSCs via Fas/FasL pathway could increase number of osteoclast in giant cell tumor of jaw (JGCT).Compared to jaw bone marrow mesenchymal stem cells (JBMSCs), we will ascertain the induction of CD14+ macrophage apoptosis by GMSCs, the induction of CD14+ macrophage apoptosis by GMSCs via Fas/FasL pathway and its molecular mechanism. Finally, we will document the hypothesis in animal model. Through above studies, we will discuss the role and molecular mechanism of Fas/FasL which play in the regulation of pre-osteoclast apoptosis by MSCs and pathogenesis of giant cell tumor of jaw. The aim of this study is exploring the new mechanism of bone destruction by MSCs in JGCT and providing the new concept that Fas/FasL as a target for the treatment of JGCT from the point of translational medicine.

英文关键词： cell apoptosis;mesenchymal stem cell;stem cell differentiation