Alteration of Notch signaling in skeletal development and disease
Alteration of Notch signaling in skeletal development and disease
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DOI：
10.1111/j.1749-6632.2009.05307.x
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发表时间：
2010-01-01
期刊：
影响因子：
--
通讯作者：
Lee, Brendan
中科院分区：
文献类型：
--
作者：
Tao, Jianning;Chen, Shan;Lee, Brendan
Notch信号转导是一种进化上保守的机制，用于指定和调节器官发生和组织更新。人类和小鼠的遗传学研究已经证明了Notch信号通路的许多组分中的突变导致骨骼模式缺陷。最近，Notch信号传导对成骨细胞特化、增殖和分化的体内作用除了其对破骨细胞活性的调节之外已经被证明。然而，虽然我们对骨骼生物学中经典Notch信号的理解正在迅速发展，但对非经典Notch信号的作用仍然知之甚少。在病理学背景下，Notch信号传导的畸变也与骨肉瘤相关。这些研究提出了Notch如何与其他信号通路（如Wnt）相互作用的问题。最后，由于间充质干细胞和成骨细胞分化期间Notch信号传导的时间和背景依赖性，因此用于骨相关疾病的Notch信号传导的操纵仍然复杂。
Notch signaling is an evolutionarily conserved mechanism for specifying and regulating organogenesis and tissue renewal. Human and mouse genetic studies have demonstrated mutations in many components of the Notch signaling pathway that cause skeletal patterning defects. More recently, the in vivo effects of Notch signaling on osteoblast specification, proliferation, and differentiation have been demonstrated in addition to its regulation of osteoclast activity. However, while our understanding of canonical Notch signaling in skeletal biology is rapidly evolving, the role of noncanonical Notch signaling is still poorly understood. In a pathologic context, aberration of Notch signaling is also associated with osteosarcoma. These studies raise the question of how Notch may interact with other signaling pathways, such as Wnt. Finally, manipulation of Notch signaling for bone-related diseases remains complex because of the temporal and context-dependent nature of Notch signaling during mesenchymal stem cell and osteoblast differentiation.