Rescue of Premature Coronal Suture Fusion with TGF-β2 Neutralizing Antibody in Rabbits with Delayed-Onset Synostosis

Abstract

Objectives:

An overexpression of Tgf-β2 leads to calvarial hyperostosis and suture fusion in individuals with craniosynostosis. Inhibition of Tgf-β2 may help rescue fusing sutures and restore normal growth. The present study was designed to test this hypothesis.

Design:

Twenty-eight New Zealand White rabbits with delayed-onset coronal synostosis had radiopaque markers placed on either side of the coronal sutures at 10 days of age. The rabbits were randomly assigned to: (1) sham control rabbits (n = 10), (2) rabbits with control IgG (100 μg/suture) delivered in a collagen vehicle (n = 9), and (3) rabbits with Tgf-β2 neutralizing antibody (100 μg/suture) delivered in a collagen vehicle (n = 9). Longitudinal growth data were collected at 10, 25, 42, and 84 days of age. Sutures were harvested at 84 days of age for histomorphometry.

Results:

Radiographic analysis showed significantly greater (P < .05) coronal suture marker separation, craniofacial length, cranial vault length, height, shape indices, cranial base length, and more lordotic cranial base angles in rabbits treated with anti-Tgf-β2 antibody than in controls at 42 and 84 days of age. Histologically, rabbits treated with anti-Tgf-β2 antibody at 84 days of age had patent and significantly (P < .05) wider coronal sutures and greater sutural area compared to controls.

Conclusions:

These data support our hypothesis that antagonism of Tgf-β2 may rescue fusing coronal sutures and facilitate craniofacial growth in this rabbit model. These findings also suggest that cytokine therapy may have clinical significance in infants with progressive postgestational craniosynostosis.

Keywords

craniosynostosis rabbits Tgf-β2 neutralizing antibodies craniofacial growth coronal suture

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