内皮细胞向间充质细胞转化（Endothelial-mesenchymal transition,EndMT）途径是异位骨化症（HO）重要的病理机制，而转化生长因子-β（TGF-β）信号传导途径是其公认的主要信号通路。本课题组在前期试验中证实促进TGF-β信号通路中的Smad-7基因表达上调，可有效抑制EndMT途径，阻滞HO进展。因此我们提出如下假说：采用纳米壳聚糖颗粒作为Smad-7基因载体，CD34抗体作为配体构建的Smad-7pDNA/壳聚糖纳米颗粒，能够在组织局部显著抑制EndMT和HO的进展。本研究拟通过体内和体外实验初步验证该假说，同时也在细胞、组织和动物水平进一步探讨TGF-β信号通路和EndMT途径以及HO三者之间的相互作用及其分子机制，包括影响TGF-β信号途径的下游信号通路和特定miRNA等。通过本研究将进一步明确HO的分子病理机制，为临床防治工作提供新的思路。

Endothelial-mesenchymal transition(EndMT) is an important pathological mechanismof heterotopic ossification(HO),and TGF-β signal transduction pathway is recognized as the main signal transduction pathway in this disease.Our research team has proved that EndMT as well as HO could be inhibited by over-expression of Smad-7 gene which exists in the TGF-β signal transduction pathway in the previous.study. So we put forward the following hypothesis : EndMT and HO in the local tissue could be inhibited by the combinated construction of nano chitosan particle and Smad-7 pDNA which is modified by CD-34 antibody on the surface.This study intends to validate the hypothesis preliminary by in vivo and in vitro experiments,also further discuss the mutual interaction and molecular mechanism between T-tGFβ and EndMT as well as HO in level of In cells, tissues and animals,including the downstream signal and special miRNA of TGF-β signal transduction pathway.The proposed study will clarify the molecular mechanism of HO and lead to new strategy for prevention and treatment of HO.