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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Noggin underexpression and runx-2 overexpression in a craniosynostosis rabbit model.

INTRODUCTION: Normal suture fusion has been shown to be driven by the molecular signals elucidated by the underlying dura. However, the pathogenesis of suture fusion in craniosynostosis is not well described. The purpose of our study was to examine the expression patterns of 2 important molecular signals (Noggin and Runx-2) in a cohort of congenital craniosynostotic rabbits to gain a better understanding of suture behavior in craniosynostosis. METHODS: Coronal (fusing) and sagittal (patent) rabbit cranial sutures from a colony of congenitally synostosed rabbits and wild-type (control) rabbits were harvested at a neonatal time point. These sections were then grown in organ culture and harvested for histology at 0, 7, or 14 days of culture. Fusion percentage was then assessed and an overall fusion score was calculated. Expression of Noggin and Runx-2 was then localized by immunohistochemistry and quantified by Western blot analysis. RESULTS: Histology of the wild-type cranial sutures (control) showed suture patency (score of 0%) for all coronal and sagittal sutures at 0 days, 7 days, and 14 days of organ culture. Sagittal sutures of craniosynostotic animals also showed suture patency (score of 0%) at all culture times (0, 7, and 14 days). Of the 18 coronal sutures from the craniosynostotic animals, 8 remained patent and 10 fused. For the coronal sutures that fused, fusion scores of 14%, 41%, and 84% were documented at 0, 7, and 14 days of organ culture, respectively. With immunolocalization, Noggin was found to be expressed in both the dura and suture cells underlying patent sutures, but not in fusing sutures in vitro. Runx-2 was found to be expressed in the dura beneath the suture and suture cells of fusing sutures, not patent sutures. Western blot densitometry confirmed these findings. CONCLUSIONS: Our results suggest that pathologic rabbit coronal sutures progressed toward complete suture fusion in vitro, and expression patterns of Noggin and Runx-2 paralleled that of a well-studied normal suture fusion model.[1]


  1. Noggin underexpression and runx-2 overexpression in a craniosynostosis rabbit model. Gabbay, J.S., Heller, J., Spoon, D.B., Mooney, M., Acarturk, O., Askari, M., Wasson, K.L., Bradley, J.P. Annals of plastic surgery. (2006) [Pubmed]
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