Overexpression of Nell-1, a craniosynostosis-associated gene, induces apoptosis in osteoblasts during craniofacial development
Overexpression of Nell-1, a craniosynostosis-associated gene, induces apoptosis in osteoblasts during craniofacial development
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DOI：
10.1359/jbmr.2003.18.12.2126
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发表时间：
2003-12-01
影响因子：
6.2
通讯作者：
Ting, K
中科院分区：
文献类型：
--
作者：
Zhang, XL;Carpenter, D;Ting, K
介绍：颅缝早闭（CS）是最常见的先天性颅面畸形之一，是颅缝过早闭合。以前，我们报道了NELL-1作为一种新的分子在CS患者的颅缝过早闭合过程中过表达。在啮齿动物模型中，Nell-1过表达诱导颅骨过度生长并导致过早缝合。在细胞水平上，Nell-1被认为可以促进成骨细胞的分化。材料和方法：通过病毒感染和重组蛋白将不同水平的Nell-1导入成骨细胞。进行细胞凋亡和基因表达测定。过表达Nell-1的小鼠进行了检查apoptosis.Results：在这份报告中，我们进一步表明，过表达Nell-1诱导细胞凋亡，沿着与凋亡相关基因的调制。仅在成骨细胞中观察到Nell-1诱导的凋亡，而在NIH 3 T3或原代成纤维细胞中未观察到。CS小鼠模型过表达Nell-1表现出细胞凋亡水平的增加在calvaria.Conclusion：我们表明，Nell-1的表达调节颅骨成骨细胞分化和凋亡途径。Nell-1过表达破坏了这些通路，导致颅面异常，如过早缝合。
Introduction: Craniosynostosis (CS), one of the most common congenital craniofacial deformities, is the premature closure of cranial sutures. Previously, we reported NELL-1 as a novel molecule overexpressed during premature cranial suture closure in patients with CS. Nell-1 overexpression induced calvarial overgrowth and resulted in premature suture closure in a rodent model. On a cellular level, Nell-1 is suggested to promote osteoblast differentiation.Materials and Methods: Different levels of Nell-1 were introduced into osteoblastic cells by viral infection and recombinant protein. Apoptosis and gene expression assays were performed. Mice overexpressing Nell-1 were examined for apoptosis.Results: In this report, we further showed that overexpression of Nell-1 induced apoptosis along with modulation of apoptosis-related genes. The induction of apoptosis by Nell-1 was observed only in osteoblastic cells and not in NIH3T3 or primary fibroblasts. The CS mouse model overexpressing Nell-1 showed increased levels of apoptosis in the calvaria.Conclusion: We show that Nell-1 expression modulates calvarial osteoblast differentiation and apoptosis pathways. Nell-1 overexpression disrupts these pathways resulting in craniofacial anomalies such as premature suture closure.