Anti-TGF-beta2 antibody therapy inhibits postoperative resynostosis in craniosynostotic rabbits

Plast Reconstr Surg. 2007 Apr 1;119(4):1200-1212. doi: 10.1097/01.prs.0000258403.49584.ec.

Abstract

Background: Postoperative resynostosis is a common clinical finding. It has been suggested that an overexpression of transforming growth factor (TGF)-beta2 may be related to craniosynostosis and may contribute to postoperative resynostosis. Interference with TGF-beta2 function with the use of neutralizing antibodies may inhibit resynostosis. The present study was designed to test this hypothesis.

Methods: New Zealand White rabbits with bilateral coronal suture synostosis were used as suturectomy controls (group 1, n = 9) or given suturectomy with nonspecific, control immunoglobulin G antibody (group 2, n = 9) or suturectomy with anti-TGF-beta2 antibody (group 3, n = 11). At 10 days of age, a 3 x 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slowly resorbing collagen gel mixed with either immunoglobulin G (100 mug per suture) or anti-TGF-beta2 (100 mug per suture). Three-dimensional computed tomography scan reconstructions of the defects were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histomorphometric analysis.

Results: Computed tomography scan data revealed that the suturectomy sites treated with anti-TGF-beta2 showed significantly (p < 0.05) greater areas through 84 days of age compared with controls. Histomorphometry also showed that suturectomy sites treated with anti-TGF-beta2 had patent suturectomy sites and more fibrous tissue in the defects compared with sites in control rabbits and had significantly (p < 0.001) less new bone area (by approximately 215 percent) in the suturectomy site.

Conclusions: These data support the initial hypothesis that interference with TGF-beta2 function inhibited postoperative resynostosis in this rabbit model. They also suggest that this biologically based therapy may be a potential surgical adjunct to retard postoperative resynostosis in infants with craniosynostosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology
  • Cephalometry
  • Cranial Sutures / drug effects*
  • Cranial Sutures / growth & development
  • Craniosynostoses / prevention & control*
  • Disease Models, Animal
  • Female
  • Immunohistochemistry
  • Injections, Intralesional
  • Male
  • Rabbits
  • Random Allocation
  • Reference Values
  • Secondary Prevention
  • Sensitivity and Specificity
  • Skull / growth & development
  • Synostosis / prevention & control
  • Transforming Growth Factor beta2 / antagonists & inhibitors*
  • Transforming Growth Factor beta2 / pharmacology*

Substances

  • Antibodies
  • Transforming Growth Factor beta2