Blood flow controls bone vascular function and osteogenesis.
Blood flow controls bone vascular function and osteogenesis.
复制标题
DOI：
10.1038/ncomms13601
复制
发表时间：
2016-12-06
影响因子：
16.6
通讯作者：
Adams, Ralf H.
中科院分区：
文献类型：
--
作者：
Ramasamy, Saravana K.;Kusumbe, Anjali P.;Schiller, Maria;Zeuschner, Dagmar;Bixel, M. Gabriele;Milia, Carlo;Gamrekelashvili, Jaba;Limbourg, Anne;Medvinsky, Alexander;Santoro, Massimo M.;Limbourg, Florian P.;Adams, Ralf H.
虽然血管在骨稳态和修复中发挥重要作用，但骨骼系统中血管功能的基本方面仍然知之甚少。在这里，我们表明，长骨血管系统产生一个特殊的流动模式，这是重要的适当的血管生成。活体成像显示，小鼠长骨中的血管生长涉及内皮芽的延伸和吻合融合。血流受损导致血管生成和骨生成缺陷，以及内皮细胞中Notch信号转导的下调。在老年小鼠中，骨骼血流量和内皮Notch活性也降低，导致血管生成和骨生成减少，这通过Notch的遗传再激活而恢复。老年小鼠中的血流量和血管生成也在施用双膦酸盐时增强，双膦酸盐是一类经常用于治疗骨质疏松症的药物。我们认为血流和内皮Notch信号是控制骨骼系统衰老过程的关键因素。新血管和骨的形成是耦合的。在这里，作者表明，血流代表了骨中血管生成和内皮Notch信号传导的关键调节因子，并且老年小鼠内皮中Notch信号传导的重新激活使骨骼恢复活力。
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. Formation of new blood vessels and bone is coupled. Here the authors show that blood flow represents a key regulator of angiogenesis and endothelial Notch signalling in the bone, and that reactivation of Notch signalling in the endothelium of aged mice rejuvenates the bone.
登录
查看更多内容
影响因子：
4.4
作者：
Han, H;Tanigaki, K;Honjo, T
通讯作者：
Honjo, T
影响因子：
25
作者：
Hoeck, Joerg D.;Jandke, Anett;Behrens, Axel
通讯作者：
Behrens, Axel
影响因子：
4.1
作者：
Berendsen AD;Olsen BR
通讯作者：
Olsen BR
DOI：
10.1161/atvbaha.114.303218
发表时间：
2014-11-01
影响因子：
8.7
作者：
Corada, Monica;Morini, Marco Francesco;Dejana, Elisabetta
通讯作者：
Dejana, Elisabetta
影响因子：
64.8
作者：
通讯作者：
--