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.
Nat Commun. 2016 Dec 6;7:13601. doi: 10.1038/ncomms13601.
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.
虽然血管在骨骼的稳态和修复中起着重要作用，但骨骼系统中血管功能的基本方面仍知之甚少。在这里，我们表明长骨的脉管系统产生了一种特殊的流动模式，这对于适当的血管生成很重要。活体成像显示，在小鼠长骨中，血管生长涉及内皮芽的延伸和吻合融合。血流受损会导致血管生成和骨生成缺陷，并导致内皮细胞中的 Notch 信号下调。在老年小鼠中，骨骼血流和内皮 Notch 活性也降低，导致血管生成和骨生成减少，而通过 Notch 的遗传再激活可逆转这种减少。在给予双膦酸盐（一种常用于治疗骨质疏松症的药物）时，老年小鼠的血流和血管生成也会增强。我们提出，血流和内皮 Notch 信号是控制骨骼系统衰老过程的关键因素。
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