Anti-TGF-beta2 antibody therapy inhibits postoperative resynostosis in craniosynostotic rabbits.
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.
Mooney
Mark P
MP
Pittsburgh, Pa.; Chapel Hill, N.C.; Columbus, Ohio; Los Angeles, Calif.; Ankara, Turkey; and Dallas, Texas From the Departments of Oral Medicine and Pathology, Anthropology, Plastic and Reconstructive Surgery, Orthodontics, and Orthopedic Surgery, the Cleft Palate-Craniofacial Center, and the School of Dental Medicine, University of Pittsburgh; the Department of Plastic Surgery, School of Medicine, University of North Carolina; Department of Pediatric Dentistry, College of Dentistry, Ohio State University; Division of Plastic and Reconstructive Surgery, University of California, Los Angeles; Division of Plastic Surgery, University of Pittsburgh Medical Center; Department of Plastic and Reconstructive Surgery, Gülhane Military Medical Academy; and Department of Biomedical Sciences, Baylor College of Dentistry, Texas A & M University System Health Science Center.
Losken
H Wolfgang
HW
Moursi
Amr M
AM
Bradley
James
J
Azari
Kodi
K
Acarturk
T Oguz
TO
Cooper
Gregory M
GM
Thompson
Brian
B
Opperman
Lynne A
LA
Siegel
Michael I
MI
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D002508:Cephalometry; D003393:Cranial Sutures / Q000187:drug effects* / Q000254:growth & development; D003398:Craniosynostoses / Q000517:prevention & control*; D004195:Disease Models, Animal; D005260:Female; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008297:Male; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D055502:Secondary Prevention; D012680:Sensitivity and Specificity; D012886:Skull / Q000254:growth & development; D013580:Synostosis / Q000517:prevention & control; D053781:Transforming Growth Factor beta2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*
D000906:Antibodies; D053781:Transforming Growth Factor beta2