The authors have no conflict of interest.
Overexpression of Nell-1, a Craniosynostosis-Associated Gene, Induces Apoptosis in Osteoblasts During Craniofacial Development†
Article first published online: 1 DEC 2003
Copyright © 2003 ASBMR
Journal of Bone and Mineral Research
Volume 18, Issue 12, pages 2126–2134, December 2003
How to Cite
Zhang, X., Carpenter, D., Bokui, N., Soo, C., Miao, S., Truong, T., WU, B., Chen, I., Vastardis, H., Tanizawa, K., Kuroda, S. and Ting, K. (2003), Overexpression of Nell-1, a Craniosynostosis-Associated Gene, Induces Apoptosis in Osteoblasts During Craniofacial Development. J Bone Miner Res, 18: 2126–2134. doi: 10.1359/jbmr.2003.18.12.2126
- Issue published online: 2 DEC 2009
- Article first published online: 1 DEC 2003
- Manuscript Accepted: 30 JUL 2003
- Manuscript Revised: 18 MAY 2003
- Manuscript Received: 3 FEB 2003
We studied the cellular function of Nell-1, a craniosynostosis-related gene, in craniofacial development. Nell-1 modulates calvarial osteoblast differentiation and apoptosis pathways. Nell-1 overexpression disrupts these pathways resulting in craniofacial anomalies such as premature suture closure.
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.