Communication between osteoblasts and endothelial cells (ECs) is essential for bone turnover, but the molecular mechanisms of such communication are not well defined. Here we identify Cxcl9 as an angiostatic factor secreted by osteoblasts in the bone marrow microenvironment. We show that Cxcl9 produced by osteoblasts interacts with vascular endothelial growth factor and prevents its binding to ECs and osteoblasts, thus abrogating angiogenesis and osteogenesis both in mouse bone and in vitro. The mechanistic target of rapamycin complex 1 activates Cxcl9 expression by transcriptional upregulation of STAT1 and increases binding of STAT1 to the Cxcl9 promoter in osteoblasts. These findings reveal the essential role of osteoblast-produced Cxcl9 in angiogenesis and osteogenesis in bone, and Cxcl9 can be targeted to elevate bone angiogenesis and prevent bone loss-related diseases.

中文翻译：

---

成骨细胞分泌Cxcl9来调节骨骼中的血管生成。

成骨细胞与内皮细胞（EC）之间的通讯对于骨转换至关重要，但这种通讯的分子机制尚不明确。在这里，我们确定Cxcl9为骨髓微环境中成骨细胞分泌的血管抑制因子。我们显示，由成骨细胞产生的Cxcl9与血管内皮生长因子相互作用，并阻止其与EC和成骨细胞的结合，从而在小鼠骨骼和体外均消除血管生成和成骨作用。雷帕霉素复合物1的机械目标通过STAT1的转录上调激活Cxcl9表达，并增加成骨细胞中STAT1与Cxcl9启动子的结合。这些发现揭示了成骨细胞产生的Cxcl9在骨骼的血管生成和成骨中的重要作用，