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Overexpression of Nell‐1 , a Craniosynostosis‐Associated Gene, Induces Apoptosis in Osteoblasts During Craniofacial Development
Author(s) -
Zhang Xinli,
Carpenter Dale,
Bokui Nobuyuki,
Soo Chia,
Miao Steve,
Truong Thien,
WU Benjamin,
Chen Ingrid,
Vastardis Heleni,
Tanizawa Katsuyuki,
Kuroda Shun″Ichi,
Ting Kang
Publication year - 2003
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2003.18.12.2126
Subject(s) - craniosynostosis , calvaria , osteoblast , craniofacial , apoptosis , biology , microbiology and biotechnology , anatomy , genetics , in vitro
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.