Craniofacial Growth Following Anti-Tgf-Β2 Therapy in Rabbits with Unicoronal Synostosis

Objectives: Studies have shown that the expression of the various Transforming Growth Factor-bs (Tgf-b) isoforms control normal cranial development and fusion. It has been suggested that over-expression of Tgf-b2 causes craniosynostosis, resynostosis, and asymmetry in cases of unicoronal synostosis (UCS). Anti-Tgf-b2 antibody may prevent resynostosis and facilitate symmetrical growth. The present study tests this hypothesis in a rabbit model of UCS.

Methods: Twenty-six, New Zealand white rabbits with UCS were divided into 3 groups: 1) Suturectomy control (n=9); 2) Suturectomy with non-specific, control IgG antibody in a slow release collagen vehicle, (n=9); and 3) Suturectomy with anti-Tgf-b2 antibody in a slow release collagen vehicle (n=8). At 10 days of age, a 3mm x 7mm coronal suturectomy was performed on the synostosed side. The sites in Groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing, collagen gel mixed with either IgG antibody (100µg/suture) or anti-Tgf-b2 antibody (100µg/suture). Serial CT scans and cephalographs were taken at 10, 25, 42, and 84 days of age. Defect areas and 32 craniofacial measurements were obtained. Mean differences were analyzed using a 3x1 (group by single age) ANOVA.

Results: Analysis of the CT scan data revealed that anti-Tgf-b2 treated rabbits had significantly greater (F=3.63; P<0.05) defect areas at 25 days of age compared to untreated and IgG controls. No significant group differences were noted at any other time periods. Radiograph data analysis revealed significant (p<0.05) compensatory growth changes in the frontonasal, coronal, and anterior lambdoidal sutures as well as the anterior cranial base from 42-84 days in the rabbits treated with anti-TGF-b2 compared to controls.

Conclusions: These data support the hypothesis that anti-Tgf-b2 therapy inhibits post-operative resynostosis and facilitates vault and base growth. These findings suggest that this cytokine therapy may have potential clinical use to prevent postoperative resynostosis.

NIDCR (DE13078)