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Blood flow controls bone vascular function and osteogenesis

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  • Saravana K. Ramasamy

    (Faculty of Medicine, Max-Planck-Institute for Molecular Biomedicine and University of Münster
    Research group Integrative Skeletal Physiology, Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, Du Cane Road)

  • Anjali P. Kusumbe

    (Faculty of Medicine, Max-Planck-Institute for Molecular Biomedicine and University of Münster
    Research group Tissue and Tumor Microenvironments, Kennedy Institute of Rheumatology, University of Oxford)

  • Maria Schiller

    (Faculty of Medicine, Max-Planck-Institute for Molecular Biomedicine and University of Münster)

  • Dagmar Zeuschner

    (Electron Microscopy Unit, Max-Planck-Institute for Molecular Biomedicine)

  • M. Gabriele Bixel

    (Faculty of Medicine, Max-Planck-Institute for Molecular Biomedicine and University of Münster)

  • Carlo Milia

    (VIB Vesalius Research Center, KU Leuven)

  • Jaba Gamrekelashvili

    (Hannover Medical School)

  • Anne Limbourg

    (Hannover Medical School)

  • Alexander Medvinsky

    (Research group Ontogeny of Haematopoietic Stem Cells, MRC Centre for Regenerative Medicine, University of Edinburgh)

  • Massimo M. Santoro

    (VIB Vesalius Research Center, KU Leuven
    Molecular Biotechnology Center, University of Torino)

  • Florian P. Limbourg

    (Hannover Medical School)

  • Ralf H. Adams

    (Faculty of Medicine, Max-Planck-Institute for Molecular Biomedicine and University of Münster)

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.

Suggested Citation

  • Saravana K. Ramasamy & Anjali P. Kusumbe & Maria Schiller & Dagmar Zeuschner & M. Gabriele Bixel & Carlo Milia & Jaba Gamrekelashvili & Anne Limbourg & Alexander Medvinsky & Massimo M. Santoro & Flori, 2016. "Blood flow controls bone vascular function and osteogenesis," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13601
    DOI: 10.1038/ncomms13601
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