Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone
Bin Huang(Third Affiliated Hospital of Southern Medical University), Wenhao Wang(Third Affiliated Hospital of Southern Medical University), Qingchu Li(Third Affiliated Hospital of Southern Medical University), Zhenyu Wang(Third Affiliated Hospital of Southern Medical University), Bo Yan(Third Affiliated Hospital of Southern Medical University), Zhongmin Zhang(Third Affiliated Hospital of Southern Medical University), Liang Wang(Third Affiliated Hospital of Southern Medical University), Minjun Huang(Third Affiliated Hospital of Southern Medical University), Chunhong Jia(Southern Medical University), Jiansen Lu(Third Affiliated Hospital of Southern Medical University), Sichi Liu(Southern Medical University), Hongdong Chen(Southern Medical University), Mangmang Li(Southern Medical University), Daozhang Cai(Third Affiliated Hospital of Southern Medical University), Yu Jiang(University of Pittsburgh), Dadi Jin(Third Affiliated Hospital of Southern Medical University), Xiaochun Bai(Third Affiliated Hospital of Southern Medical University)
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.