Jagged1 is essential for osteoblast development during maxillary ossification.

Jagged1 is essential for osteoblast development during maxillary ossification.
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DOI:
10.1016/j.bone.2014.01.019
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发表时间:
2014-05
期刊:
影响因子:
4.1
通讯作者:
Goudy, Steven L.
Goudy, Steven L.
中科院分区:
医学2区
文献类型:
--
作者:
Hill, Cynthia R.;Yuasa, Masato;Schoenecker, Jonathan;Goudy, Steven L.

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上颌骨发育不全是由于上颌骨膜内骨化不充分,导致牙齿咬合不佳,呼吸道阻塞和美容畸形。使用Wnt 1-cre; Jagged 1f/f(Jag 1CKO)在颅神经嵴(CNC)细胞中条件性缺失Jagged 1(Jag 1)导致上颌骨发育不全,其特征在于使用μCT评价的骨形态和密度的内在差异。Jag 1CKO上颌骨改变了胶原沉积,延迟骨化,并减少表达的早期和晚期成骨细胞发育的决定因素在上颌骨骨化。在Jag 1CKO小鼠胚胎上颌骨间充质(MEMM)细胞的体外骨培养证明矿化减少,这也与成骨细胞决定簇的诱导减少有关。BMP受体表达失调的Jag 1CKO MEMM细胞表明,这些细胞不能响应BMP诱导的分化。JAG 1-Fc挽救了体外矿化和成骨细胞基因表达的变化。这些数据表明,JAG 1信号在CNC衍生的MEMM细胞所需的成骨细胞的发育和分化在上颌骨骨化。
Maxillary hypoplasia occurs due to insufficient maxillary intramembranous ossification, leading to poor dental occlusion, respiratory obstruction and cosmetic deformities. Conditional deletion of Jagged1 (Jag1) in cranial neural crest (CNC) cells using Wnt1-cre; Jagged1f/f (Jag1CKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using μCT evaluation. Jag1CKO maxillas had altered collagen deposition, delayed ossification, and reduced expression of early and late determinants of osteoblast development during maxillary ossification. In vitro bone cultures on Jag1CKO mouse embryonic maxillary mesenchymal (MEMM) cells demonstrated decreased mineralization that was also associated with diminished induction of osteoblast determinants. BMP receptor expression was dysregulated in the Jag1CKO MEMM cells suggesting that these cells were unable to respond to BMP-induced differentiation. JAG1-Fc rescued in vitro mineralization and osteoblast gene expression changes. These data suggest that JAG1 signaling in CNC-derived MEMM cells is required for osteoblast development and differentiation during maxillary ossification.
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