Rescue of coronal suture fusion using transforming growth factor-beta 3 (Tgf-beta 3) in rabbits with delayed-onset craniosynostosis.
Craniosynostosis results in cranial deformities and increased intracranial pressure, which pose extensive and recurrent surgical management problems. Developmental studies in rodents have shown that low levels of transforming growth factor-beta 3 (Tgf-beta 3) are associated with normal fusion of the interfrontal (IF) suture, and that Tgf-beta 3 prevents IF suture fusion in a dose-dependent fashion. The present study was designed to test the hypothesis that Tgf-beta 3 can also prevent or "rescue" fusing sutures in a rabbit model with familial craniosynostosis. One hundred coronal sutures from 50 rabbits with delayed-onset, coronal suture synostosis were examined in the present study. The rabbits were divided into five groups of 10 rabbits each: 1) sham controls, 2) bovine serum albumin (BSA, 500 ng) low-dose protein controls, 3) low-dose Tgf-beta 3 (500 ng), 4) high-dose BSA (1,000 ng) controls, and 5) high-dose Tgf-beta 3 (1,000 ng). At 10 days of age, radiopaque amalgam markers were implanted in all of the rabbits on either side of the coronal suture to monitor sutural growth. At 25 days of age, the BSA or Tgf-beta 3 was combined with a slow-absorbing collagen vehicle and injected subperiosteally above the coronal suture. Radiographic results revealed that high-dose Tgf-beta 3 rabbits had significantly greater (P < 0.05) coronal suture marker separation than the other groups. Histomorphometric analysis revealed that high-dose Tgf-beta 3 rabbits also had patent coronal sutures and significantly (P < 0.01) greater sutural widths and areas than the other groups. The results suggest that there is a dose-dependent effect of TGF-beta 3 on suture morphology and area in these rabbits, and that the manipulation of such growth factors may have clinical applications in the treatment of craniosynostosis.
Chong
Sherri Lyn
SL
Department of Oral Medicine and Pathology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Mitchell
Ronal
R
Moursi
Amr M
AM
Winnard
Phillip
P
Losken
H Wolfgang
HW
Bradley
James
J
Ozerdem
Omer R
OR
Azari
Kodi
K
Acarturk
Oguz
O
Opperman
Lynne A
LA
Siegel
Michael I
MI
Mooney
Mark P
MP
D000818:Animals; D000831:Animals, Newborn; D003393:Cranial Sutures / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D003398:Craniosynostoses / Q000000981:diagnostic imaging / Q000473:pathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D011817:Rabbits; D011859:Radiography; D016212:Transforming Growth Factor beta / Q000627:therapeutic use*; D053782:Transforming Growth Factor beta3
D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3