Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.
Coupling of angiogenesis and osteogenesis by a specific vessel subtype in bone.
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DOI：
10.1038/nature13145
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发表时间：
2014-03-20
期刊：
影响因子：
64.8
通讯作者：
Adams RH
中科院分区：
文献类型：
--
作者：
Kusumbe AP;Ramasamy SK;Adams RH
哺乳动物骨骼系统具有维持终身骨形成的间充质干细胞、骨祖细胞和成骨细胞的分级系统。骨生成对于骨的稳态更新以及再生性骨折愈合是必不可少的，但是这些过程在老化的生物体中经常下降，导致骨量损失和骨折发生率增加。有证据表明，骨中血管的生长和骨生成是耦合的，但对潜在的细胞和分子机制知之甚少。在这里，我们确定了一个新的毛细血管亚型在小鼠骨骼系统具有独特的形态，分子和功能特性。这些血管存在于特定位置，介导骨血管系统的生长，产生不同的代谢和分子微环境，维持血管周围的骨祖细胞，并将血管生成与骨生成偶联。这些血管和相关的骨祖细胞的丰度在老年动物的骨中强烈减少，这是可逆的以恢复骨量。
The mammalian skeletal system harbours a hierarchical system of mesenchymal stem cells, osteoprogenitors and osteoblasts sustaining lifelong bone formation. Osteogenesis is indispensable for the homeostatic renewal of bone as well as regenerative fracture healing, but these processes frequently decline in ageing organisms leading to loss of bone mass and increased fracture incidence. There is evidence indicating that the growth of blood vessels in bone and osteogenesis are coupled, but relatively little is known about the underlying cellular and molecular mechanisms. Here we identify a new capillary subtype in the murine skeletal system with distinct morphological, molecular and functional properties. These vessels are found in specific locations, mediate growth of the bone vasculature, generate distinct metabolic and molecular microenvironments, maintain perivascular osteoprogenitors, and couple angiogenesis to osteogenesis. The abundance of these vessels and associated osteoprogenitors was strongly reduced in bone from aged animals, which was pharmacologically reversible to restore bone mass.