Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone

Bin Huang, Wenhao Wang, Qingchu Li, Zhenyu Wang, Bo Yan, Zhongmin Zhang, Liang Wang, Minjun Huang, Chunhong Jia, Jiansen Lu, Sichi Liu, Hongdong Chen, Mangmang Li, Daozhang Cai, Yu Jiang, Dadi Jin () and Xiaochun Bai ()
Additional contact information
Bin Huang: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Wenhao Wang: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Qingchu Li: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Zhenyu Wang: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Bo Yan: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Zhongmin Zhang: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Liang Wang: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Minjun Huang: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Chunhong Jia: State Key Laboratory of Organ Failure Research, School of Basic Medical Science, Southern Medical University
Jiansen Lu: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Sichi Liu: State Key Laboratory of Organ Failure Research, School of Basic Medical Science, Southern Medical University
Hongdong Chen: State Key Laboratory of Organ Failure Research, School of Basic Medical Science, Southern Medical University
Mangmang Li: State Key Laboratory of Organ Failure Research, School of Basic Medical Science, Southern Medical University
Daozhang Cai: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Yu Jiang: University of Pittsburgh School of Medicine
Dadi Jin: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University
Xiaochun Bai: Academy of Orthopedics, Guangdong Province, The Third Affiliated Hospital, Southern Medical University

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: Abstract 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.

Date: 2016
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DOI: 10.1038/ncomms13885

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