{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T22:17:56Z","timestamp":1767651476094},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2003,12,1]],"date-time":"2003-12-01T00:00:00Z","timestamp":1070236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1359\/jbmr.2003.18.12.2126","type":"journal-article","created":{"date-parts":[[2006,4,27]],"date-time":"2006-04-27T05:47:03Z","timestamp":1146116823000},"page":"2126-2134","source":"Crossref","is-referenced-by-count":51,"title":["Overexpression of <i>Nell-1<\/i>, a Craniosynostosis-Associated Gene, Induces Apoptosis in Osteoblasts During Craniofacial Development"],"prefix":"10.1093","volume":"18","author":[{"given":"Xinli","family":"Zhang","sequence":"first","affiliation":[{"name":"Dental and Craniofacial Research Institute, University of California at Los Angeles, Los Angeles, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dale","family":"Carpenter","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California at Irvine, Irvine, California, 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