Notch in skeletal physiology and disease.
Notch in skeletal physiology and disease.
复制标题
骨骼生理和疾病的缺口。
DOI：
10.1007/s00198-018-4694-3
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Canalis E
中科院分区：
文献类型：
--
作者：
Canalis E
Notch（Notch 1 至 4）是跨膜受体，在细胞分化和功能中发挥重要作用。 Notch受体在与其邻近细胞中的配体相互作用后被激活。有五种经典配体，称为 Jagged (Jag)1 和 Jag2，以及 Delta 样 (Dll)1、Dll3 和 Dll4。最近的工作已将Notch确定为一种信号通路，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发挥着关键作用。 Notch 的作用取决于细胞环境，四种 Notch 受体在骨骼中执行特定的功能。 Notch 信号通路成分的功能获得和丧失突变会导致多种具有明显颅面和骨骼表现的先天性疾病。 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 信号传导的改变与骨肉瘤以及乳腺癌和前列腺癌的转移潜力相关。控制Notch信号传导可能对Notch功能获得性疾病和特定的骨骼疾病有用。然而，尚无有关修饰 Notch 信号传导的药物的临床数据。总之，Notch 信号传导是一种调节健康和疾病中骨骼稳态的新途径。 Notch 受体在与其邻近细胞中的配体（Jagged 和 Delta 样）相互作用后被激活。 Notch和配体由成骨细胞和破骨细胞表达并调节它们的分化和功能。因此，Notch 调节骨骼重塑，并在健康和疾病中的骨稳态中发挥重要作用。
Notch (Notch 1 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. Notch receptors are activated following interactions with their ligands (Jagged and Delta-like) in adjacent cells. Notch and ligands are expressed by osteoblasts and osteoclasts and regulate their differentiation and function. As a consequence, Notch modulates skeletal remodeling and plays an important role in bone homeostasis in health and disease.
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DOI：
10.1002/ajmg.a.36863
发表时间：
2015-03
期刊：
American journal of medical genetics. Part A
影响因子：
--
作者：
Gripp KW;Robbins KM;Sobreira NL;Witmer PD;Bird LM;Avela K;Makitie O;Alves D;Hogue JS;Zackai EH;Doheny KF;Stabley DL;Sol-Church K
通讯作者：
Sol-Church K
影响因子：
3.7
作者：
Dishowitz MI;Mutyaba PL;Takacs JD;Barr AM;Engiles JB;Ahn J;Hankenson KD
通讯作者：
Hankenson KD
影响因子：
9.8
作者：
Canalis, Ernesto
通讯作者：
Canalis, Ernesto
影响因子：
2.8
作者：
Dishowitz, Michael I.;Terkhorn, Shawn P.;Hankenson, Kurt D.
通讯作者：
Hankenson, Kurt D.
影响因子：
13.5
作者：
Emerick, KM;Rand, EB;Piccoli, DA
通讯作者：
Piccoli, DA