title: Osteoblasts secrete Cxcl9 to regulate angiogenesis in bone.
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.
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Huang
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Wenhao
authors.initials: W
authors.lastname: Wang
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Qingchu
authors.initials: Q
authors.lastname: Li
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Zhongmin
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Minjun
authors.initials: M
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Jia
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Jiansen
authors.initials: J
authors.lastname: Lu
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Sichi
authors.initials: S
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hongdong
authors.initials: H
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Mangmang
authors.initials: M
authors.lastname: Li
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Daozhang
authors.initials: D
authors.lastname: Cai
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.
authors.forename: Dadi
authors.initials: D
authors.lastname: Jin
authors.affiliation: Academy of Orthopedics, Guangdong Province, Department of Orthopedics, The Third Affiliated Hospital, Southern Medical University, Guangzhou 510630, China.|State Key Laboratory of Organ Failure Research, Department of Cell Biology, School of Basic Medical Science, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiaochun
authors.initials: X
authors.lastname: Bai
mesh_terms: D000818:Animals; D001846:Bone Development / Q000235:genetics; D054370:Chemokine CXCL9 / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018919:Neovascularization, Physiologic; D010006:Osteoblasts / Q000378:metabolism*; D010012:Osteogenesis; D011401:Promoter Regions, Genetic; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D054370:Chemokine CXCL9; C485969:Cxcl9 protein, mouse; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D042461:Vascular Endothelial Growth Factor A