Netrins as Prophylactic Targets of Skeletal diseases: A Double-Edged Sword?
Netrins as Prophylactic Targets of Skeletal diseases: A Double-Edged Sword?
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Netrins 作为骨骼疾病的预防目标：一把双刃剑？
DOI：
10.1016/j.phrs.2017.05.011
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发表时间：
2017
影响因子：
9.3
通讯作者：
and Shizuo Akira.
中科院分区：
文献类型：
--
作者：
*Kenta Maruyama;Naoki Takemura;Mikael M. Martino;Takeshi Kondo;and Shizuo Akira.
netrin蛋白质家族参与中枢神经系统发育期间的轴突引导。在脊椎动物中，已经报道了netrin的两种膜结合形式和五种分泌形式。除了它们在神经形态发生中的关键作用之外，越来越多的报道表明netrin家族蛋白还在炎症条件、血管生成和肿瘤发生中发挥作用。在这些过程中，Unc5和DCC家族蛋白充当netrin蛋白的受体。近年来，有研究表明netrin家族的一些蛋白可能参与了骨质疏松症和关节炎等骨骼疾病的发病机制。例如，施用分泌的netrin家族蛋白如netrin 1和netrin 4在小鼠中的致病性骨降解中具有预防潜力。然而，netrin 1阻断抗体也保护小鼠免受炎症性骨破坏。因此，netrin家族蛋白参与了骨稳态的调节，但它们在骨骼系统中的作用仍存在争议。在这篇综述中，我们讨论了netrin家族蛋白质的骨天然免疫功能，并总结了其治疗潜力。
The netrin family of proteins are involved in axon guidance during central nervous system development. In vertebrates, two membrane bound forms and five secreted forms of netrin have been reported. In addition to their critical role in neural morphogenesis, a growing number of reports suggest that netrin family proteins also play a role in inflammatory conditions, angiogenesis, and tumorigenesis. In these processes, Unc5 and DCC family proteins serve as receptors of netrin proteins. Recently, it was reported that some netrin family proteins may be involved in the pathogenesis of skeletal diseases including osteoporosis and arthritis. For example, administration of secreted netrin family proteins such as netrin 1 and netrin 4 has prophylactic potential in pathogenic bone degradation in mice. However, netrin 1 blocking antibody also protects mice from inflammatory bone destruction. Therefore, netrin family proteins are involved in the regulation of bone homeostasis, but theirbona fideroles in the skeletal system remain controversial. In this review, we discuss the osteo-innate-immune functions of the netrin family of proteins, and summarize their therapeutic potential.