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Nat Commun. 2016 Dec 6;7:13601. doi: 10.1038/ncomms13601.

Blood flow controls bone vascular function and osteogenesis.

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Faculty of Medicine, Department of Tissue Morphogenesis, Max-Planck-Institute for Molecular Biomedicine and University of Münster, D-48149 Münster, Germany.
Research group Integrative Skeletal Physiology, Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK.
Research group Tissue and Tumor Microenvironments, Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7LY, UK.
Electron Microscopy Unit, Max-Planck-Institute for Molecular Biomedicine, D-48149 Münster, Germany.
VIB Vesalius Research Center, KU Leuven, 3000 Leuven, Belgium.
Department of Nephrology and Hypertension, Hannover Medical School, D-30625 Hannover, Germany.
Department of Plastic and Reconstructive Surgery, Hannover Medical School, D-30625 Hannover, Germany.
Research group Ontogeny of Haematopoietic Stem Cells, MRC Centre for Regenerative Medicine, University of Edinburgh, Edinburgh EH16 4UU, Scotland.
Molecular Biotechnology Center, Department of Molecular Biotechnology and Health Sciences, University of Torino, 10126 Torino, Italy.


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.

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