Blood flow controls bone vascular function and osteogenesis

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alendronate / pharmacology
  • Animals
  • Blood Vessels / growth & development
  • Bone and Bones / blood supply*
  • Bone and Bones / drug effects
  • Bone and Bones / physiology
  • Diphosphonates / pharmacology
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Female
  • Male
  • Mice, Inbred C57BL
  • Models, Biological
  • Neovascularization, Physiologic / drug effects
  • Osteogenesis* / drug effects
  • Receptors, Notch / metabolism
  • Regional Blood Flow / drug effects
  • Regional Blood Flow / physiology*
  • Signal Transduction / drug effects

Substances

  • Diphosphonates
  • Receptors, Notch
  • Alendronate