骨巨细胞瘤（GCT）是一种常见的侵袭性或潜在恶性骨肿瘤。迄今尚缺乏明确的发病机制及治疗靶点。本项目组前期研究发现，一种调控肿瘤细胞增殖及血管生成的细胞因子ANGPTL4在骨巨细胞瘤基质细胞（GCTSC）中表达显著增高；而骨骼系统特异性高表达ANGPTL4的转基因小鼠在16-20周龄可以自发地形成GCT样改变。我们还发现ANGPTL4可以导致单核细胞向多核破骨细胞的分化并促进骨溶解作用，同时骨基质溶解所释放的信号分子又可以促进ANGPTL4在GCTSC中的表达。因此，我们初步认为ANGPTL4在骨巨细胞瘤-骨微环境恶性循环过程中起非常重要的作用。在此基础上，本项目拟从分子、细胞水平及体内实验进一步探讨ANGPTL4调控GCTSC介导的肿瘤增殖、血管生成和骨侵蚀过程的相关机制，揭示ANGPTL4在GCT-骨微环境恶性循环形成过程中的关键作用，为GCT的治疗提供新的理论基础及药物靶点。

Giant cell tumor of bone (GCT) is a common primary invasive and potential malignant bone tumor, and the pathogenesis and therapeutic target are still unclear. Based on the previous research, we found that a kind of tumorcytosis and angiogenesis related cytokine, ANGPTL4, had an over-expression in GCT stromal cell（GCTSC）. The transgenic mice models with an up-regulation of ANGPTL4 in the skeletal system could spontaneously develop to GCT’s like change. We also found thatANGPTL4 could induce the differentiation of monocytes to osteoclasts promoting osteolysis. Meanwhile, signal molecules released by bone matrix could significantly promote the expression of ANGPTL4 in GCTSC. Therefore, we preliminarily suggested that ANGPTL4 could play a very important role in vicious cycle of bone microenvironment of GCT. On this basis, we intend to further investigating the related mechanisms about the function of ANGPTL4 on proliferation, angiogenesis and osteolysis of GCT in vitro and in vivo. Our goal is to revealing ANGPTL4’s key role in bone microenvironment vicious cycle of GCT and providing the theoretical foundation and new drug target for the treatment of GCT.