骨是乳腺癌最常见的转移部位，乳腺癌骨转移的分子机制目前尚未完全阐明。Osterix (Osx)是成骨细胞分化和骨形成中的关键转录因子。我们的前期研究结果表明：Osx在转移性高的乳腺癌细胞中高表达，在转移性低的乳腺癌细胞中不表达，且Osx显著上调MMP-9的启动子活性。生物信息学分析提示：MMP-9启动子上有3个Osx结合位点。我们用ChIP技术证明了Osx与MMP-9启动子结合。VEGF和MMP-13最近也被证明是Osx的靶基因。由此我们推测：Osx是乳腺癌骨转移的关键调节因子，它通过上调多个转移相关分子的表达而促进乳腺癌骨转移。本项目拟通过细胞实验、小鼠骨转移模型构建和临床标本检测对此假说进行验证；并运用ChIP、EMSA等技术深入探讨Osx促进乳腺癌骨转移的分子机制。本项目的研究结果不仅可以进一步丰富对Osx这个重要转录因子功能的认识，而且可以为乳腺癌骨转移的预防和治疗提供新的靶点。

Bone is the most common site of metastasis for breast cancer, however the molecular mechanism of breast cancer bone metastasis is not fully elucidated now. Osterix (Osx) is a key transcription factor required for osteoblast differentiation and bone formation. In our previous studies we found that Osx is highly expressed in metastatic breast cancer cells, while it is not expressed in breast cancer cells with low metastatic potential. We also demonstrated that the promoter activity of MMP-9 can be markedly upregulated by Osx. Bioinformatics analyses revealed that the promoter of MMP-9 has three potential binding sites of Osx. In addition, we confirmed the binding of Osx with MMP-9 promoter by ChIP assay. Recent findings revealed that VEGF and MMP-13, which are important factors involved in cancer metastasis, are target genes of Osx. Based on our findings and data from the literatures, we postulate that Osx is a key regulator of breast cancer bone metastasis and Osx promotes bone metastasis by upregulating several important molecules involved in metastasis. We will test this hypothesis using breast cancer cells and mouse bone metastatic models as well as clinical investigations. In addition, the underlying molecular mechanisms by which Osx promotes breast cancer bone metastasis will be explored by ChIP, EMSA, etc. Results of this project will not only provide new insight into the role of Osx, but also provide a novel target for the prevention and treatment of breast cancer bone metastasis.