系统炎症微环境中HMGB1对骨髓间充质干细胞信号成骨分化的调控机制研究

项目名称： 系统炎症微环境中HMGB1对骨髓间充质干细胞信号成骨分化的调控机制研究

项目编号： No.81201397

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 薛德挺

作者单位： 浙江大学

项目金额： 23万元

中文摘要： 多发伤患者由于软组织和多发骨折引起机体无菌性系统炎症反应。系统炎症引起骨折愈合延迟或骨不连，但系统炎症微环境对骨折愈合影响的机制目前尚不清楚。HMGB1是系统炎症的关键介导因子,骨髓间充质干细胞(MSC)是成骨分化的主要细胞。前期研究发现HMGB1在成骨分化不同阶段具有不同的作用，而成骨分化不同阶段MSC表面HMGB1受体表达发生改变。因此，我们提出HMGB1对成骨分化的影响是通过MSC表面HMGB1受体在成骨分化的不同阶段表达发生改变而实现的假说。为此，通过检测MSC成骨分化不同阶段HMGB1受体的表达，研究受体表达变化与成骨分化、分泌相关因子之间的时效关系；检测HMGB1作用MSC后相关信号通路改变，探讨相关机制；通过系统炎症骨折动物模型，从组织学角度阐明系统炎症微环境对骨折愈合影响机制。本研究可以为临床中多发伤、多发骨折患者的治疗和改善预后提供一定的理论和实验依据。

中文关键词： HMGB1；炎症反应；骨髓间充质干细胞；信号通路；骨折修复

英文摘要： Multiple injuries ususlly cause systematic aseptic inflammation due to soft tussue injury and multiple fractures.Systematic inflammation will delay fracture healing or cause fracture nonunion.However,the mechanism of systematic inflammation microenvironment affecting fracture healing is still unclear.HMGB1 is the key factor mediating systematic inflammation.Mesenchymal stem cells (MSC) are the main cells for osteogenesis.Our previous study found that HMGB1 had different effects on the osteogenesis of MSC in different ossification stages and the amounts of MSC expressed HMGB1 receptors were also different during different ossification stages.So we propose that the change of MSC expressed receptors for HMGB1 during different ossification stages results in the different effects of HMGB1 on osteogenesis.In order to proving our hypothesis,we will inspect the receptors of HMGB1 expression on MSC during ossification and find out the correlation between receptors expression,osteogenesis and secreted factors.We will assess the effects of HMGB1 on osteogenesis signal pathways changes and find out related mechanisms.Through fracture animal model with system inflammation, we will find out how HMGB1 in the system inflammation microenvironment influence fracture healing in tissue aspect.Our study will provde some experimental

英文关键词： HMGB1；inflamation response；MSC；signal transduction；fracture repair