Blood flow controls bone vascular function and osteogenesis
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
While blood vessels play important roles in bone homeostasis and repair, fundamental aspects of vascular function in the skeletal system remain poorly understood. Here we show that the long bone vasculature generates a peculiar flow pattern, which is important for proper angiogenesis. Intravital imaging reveals that vessel growth in murine long bone involves the extension and anastomotic fusion of endothelial buds. Impaired blood flow leads to defective angiogenesis and osteogenesis, and downregulation of Notch signalling in endothelial cells. In aged mice, skeletal blood flow and endothelial Notch activity are also reduced leading to decreased angiogenesis and osteogenesis, which is reverted by genetic reactivation of Notch. Blood flow and angiogenesis in aged mice are also enhanced on administration of bisphosphonate, a class of drugs frequently used for the treatment of osteoporosis. We propose that blood flow and endothelial Notch signalling are key factors controlling ageing processes in the skeletal system.
Date Issued
2016-12-06
Date Acceptance
2016-10-19
Citation
Nature Communications, 2016, 7 (12)
ISSN
2041-1723
Publisher
Nature Publishing Group
Journal / Book Title
Nature Communications
Volume
7
Issue
12
Copyright Statement
© 2016 The Authors. Published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Identifier
http://www.ncbi.nlm.nih.gov/pubmed/27922003
PII: ncomms13601
Subjects
Science & Technology
Multidisciplinary Sciences
Science & Technology - Other Topics
MOLECULAR REGULATION
ENDOTHELIAL-CELLS
UP-REGULATION
TIP CELLS
NOTCH
ANGIOGENESIS
PATHWAY
VEGF
DLL4
SPECIFICATION
Alendronate
Animals
Blood Vessels
Bone and Bones
Diphosphonates
Endothelial Cells
Female
Male
Mice, Inbred C57BL
Models, Biological
Neovascularization, Physiologic
Osteogenesis
Receptors, Notch
Regional Blood Flow
Signal Transduction
Bone and Bones
Blood Vessels
Endothelial Cells
Animals
Mice, Inbred C57BL
Diphosphonates
Alendronate
Signal Transduction
Osteogenesis
Regional Blood Flow
Neovascularization, Physiologic
Models, Biological
Female
Male
Receptors, Notch
Publication Status
Published
Coverage Spatial
England
Article Number
ARTN 13601