Notch (Notch1 through 4) are transmembrane receptors that play a fundamental role in cell differentiation and function. Notch receptors are activated following interactions with their ligands in neighboring cells. There are five classic ligands termed Jagged (Jag)1 and Jag2 and Delta-like (Dll)1, Dll3, and Dll4. Recent work has established Notch as a signaling pathway that plays a critical role in the differentiation and function of cells of the osteoblast and osteoclast lineages and in skeletal development and bone remodeling. The effects of Notch are cell-context dependent, and the four Notch receptors carry out specific functions in the skeleton. Gain- and loss-of-function mutations of components of the Notch signaling pathway result in a variety of congenital disorders with significant craniofacial and skeletal manifestations. The Notch ligand Jag1 is a determinant of bone mineral density, and Notch plays a role in the early phases of fracture healing. Alterations in Notch signaling are associated with osteosarcoma and with the metastatic potential of carcinoma of the breast and of the prostate. Controlling Notch signaling could prove useful in diseases of Notch gain-of-function and in selected skeletal disorders. However, clinical data on agents that modify Notch signaling are not available. In conclusion, Notch signaling is a novel pathway that regulates skeletal homeostasis in health and disease.

中文翻译：

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在骨骼生理和疾病中处于缺位状态。

Notch（Notch1至4）是跨膜受体，在细胞分化和功能中起着基本作用。Notch受体在与相邻细胞中的配体相互作用后被激活。有五个经典配体，分别称为锯齿状（Jag）1和Jag2以及类三角洲（Dll）1，Dll3和Dll4。最近的工作已将Notch确立为信号通路，在成骨细胞和破骨细胞谱系的细胞分化和功能以及骨骼发育和骨重塑中起关键作用。Notch的作用取决于细胞背景，并且四个Notch受体在骨骼中执行特定功能。Notch信号通路成分的功能获得和丧失功能突变会导致多种先天性疾病，并具有明显的颅面和骨骼表现。Notch配体Jag1是骨矿物质密度的决定因素，Notch在骨折愈合的早期阶段发挥作用。Notch信号的改变与骨肉瘤以及乳腺癌和前列腺癌的转移潜力有关。控制Notch信号传导可能在Notch功能获得性疾病和某些骨骼疾病中有用。但是，尚无有关修饰Notch信号的药物的临床数据。总之，Notch信号传导是在健康和疾病中调节骨骼稳态的新途径。控制Notch信号传导可能在Notch功能获得性疾病和某些骨骼疾病中有用。但是，尚无有关修饰Notch信号的药物的临床数据。总之，Notch信号传导是在健康和疾病中调节骨骼稳态的新途径。控制Notch信号传导可能在Notch功能获得性疾病和某些骨骼疾病中有用。但是，尚无有关修饰Notch信号的药物的临床数据。总之，Notch信号传导是在健康和疾病中调节骨骼稳态的新途径。