Hill Cynthia R, Yuasa Masato, Schoenecker Jonathan, Goudy Steven L
Department of Otolaryngology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Orthopedics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Bone. 2014 May;62:10-21. doi: 10.1016/j.bone.2014.01.019. Epub 2014 Feb 1.
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; Jagged1(f/f) (Jag1CKO) led to maxillary hypoplasia characterized by intrinsic differences in bone morphology and density using μCT evaluation. Jag1CKO maxillas revealed 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.
上颌骨发育不全是由于上颌膜内成骨不足所致,可导致牙齿咬合不良、呼吸阻塞和外观畸形。利用Wnt1-cre;Jagged1(f/f)(Jag1CKO)在颅神经嵴(CNC)细胞中条件性敲除Jagged1(Jag1),通过μCT评估导致上颌骨发育不全,其特征为骨形态和密度存在内在差异。Jag1CKO上颌骨显示胶原沉积改变、骨化延迟,以及上颌骨骨化过程中成骨细胞发育早期和晚期决定因素的表达降低。对Jag1CKO小鼠胚胎上颌间充质(MEMM)细胞进行的体外骨培养显示矿化减少,这也与成骨细胞决定因素的诱导减少有关。Jag1CKO MEMM细胞中的BMP受体表达失调,表明这些细胞无法对BMP诱导的分化作出反应。JAG1-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,CNC来源的MEMM细胞中的JAG1信号传导是上颌骨骨化过程中成骨细胞发育和分化所必需的。