| 0763 Suture Response to Noggin Protein Therapy in Rabbits with Craniosnostosis | ||
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R. HAGAN1, A.M. MOURSI2, G. KWOK1, T. BARBANO1, J. CACCAMESE1, B.J. COSTELLO1, G.M. COOPER1, J.E. LOSEE1, M.I. SIEGEL1, J. HUARD1, and M.P. MOONEY1, 1University of Pittsburgh, PA, USA, 2New York University, USA Objectives: Premature coronal suture fusion (craniosynostosis) affects 300-500 per 1,000,000 births and is associated with secondary deformities in the cranial vault and base. Faulty regulation of bone morphogenetic protein (BMP) signaling may cause calvarial bone hyperostosis and eventual fusion. Noggin is an extracellular inhibitor of BMPs. This study was designed to test the hypothesis that exogenous Noggin may help “rescue” fusing coronal sutures in a rabbit model of craniosynostosis. Methods: Twenty-eight, 25 day old, New Zealand White rabbits with delayed-onset coronal suture synostosis were randomly assigned to three groups: 1) Sham control (n=11); 2) BSA treated -protein control (10µg/suture) (n=7), and; 3) Noggin protein treated rabbits (10µg/suture) (n=10). The BSA and Noggin were mixed in a slow release (90 day) bovine collagen vehicle and injected onto each coronal suture at 25 days of age. The coronal sutures were harvested for qualitative and quantitative histological analyses at 84 days of age (an age at which > 90% of brain growth is complete). Results: Qualitative histological analysis revealed patent coronal sutures with thin osteogenic fronts and wide sutural ligaments in the Noggin treated group compared to controls. Asymmetrical differences were also seen in suture morphology between the endo- and ectocortical surfaces in Noggin treated rabbits compared to controls. Histomorphometry revealed that sutures from Noggin treated rabbits were significantly (p<0.05) wider on the ectocortical surface and significantly narrower (p<0.05) in the mesocortical region compared to controls. No significant differences (p>0.05) were noted in sutural area among groups. Conclusions: These data support our initial hypothesis that inhibition of BMP activity using Noggin therapy may rescue sutures destined to undergo premature suture fusion and suggest that Noggin may be having an inhibitory effect in a gradient through the sutural ligament. These findings may help advance our understanding of the molecular basis of craniosynostosis. DE13078, DE14342 | ||
| Seq #99 - Cranial Suture Biology 2:00 PM-3:15 PM, Thursday, March 22, 2007 Ernest N. Morial Convention Center Exhibit Hall I2-J | ||
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