Postoperative Anti-Tgf-β2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits

Mark P. Mooney, H. Wolfgang Losken, Amr Moursi, Jocelyn M. Shand, Gregory M. Cooper, Chris Curry, Lillian Ho, Anne M. Burrows, Eric J. Stelnicki, Joseph E. Losee, Lynne A. Opperman, Michael I. Siegel

Research output: Contribution to journalArticle

Abstract

Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-β2 (Tgf-β2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-β2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n = 9); 2) suturectomy with nonspecific, control IgG antibody (n = 9); and 3) suturectomy with anti-Tgf-β2 antibody (n = 11). At 10 days of age, a 3 mm × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 μg/suture) or anti-Tgf-β2 (100 μg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P < 0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. Cephalometric analysis revealed significant (P < 0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. These data support the initial hypothesis that interference with Tgf-β2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.

Original languageEnglish (US)
Pages (from-to)336-346
Number of pages11
JournalJournal of Craniofacial Surgery
Volume18
Issue number2
DOIs
StatePublished - Mar 2007

Fingerprint

Transforming Growth Factors
Rabbits
Antibodies
Growth
Sutures
Craniosynostoses
Therapeutics
Immunoglobulin G
Craniofacial Abnormalities
Tomography
Cephalometry
Synostosis
Skull Base
Neutralizing Antibodies
Skull
Collagen
Gels

Keywords

  • Craniofacial growth
  • Craniosynostosis
  • Intracranial volume
  • Neutralizing antibodies
  • Rabbits
  • Tgf-β2

ASJC Scopus subject areas

  • Surgery

Cite this

Postoperative Anti-Tgf-β2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits. / Mooney, Mark P.; Losken, H. Wolfgang; Moursi, Amr; Shand, Jocelyn M.; Cooper, Gregory M.; Curry, Chris; Ho, Lillian; Burrows, Anne M.; Stelnicki, Eric J.; Losee, Joseph E.; Opperman, Lynne A.; Siegel, Michael I.

In: Journal of Craniofacial Surgery, Vol. 18, No. 2, 03.2007, p. 336-346.

Research output: Contribution to journalArticle

Mooney, MP, Losken, HW, Moursi, A, Shand, JM, Cooper, GM, Curry, C, Ho, L, Burrows, AM, Stelnicki, EJ, Losee, JE, Opperman, LA & Siegel, MI 2007, 'Postoperative Anti-Tgf-β2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits', Journal of Craniofacial Surgery, vol. 18, no. 2, pp. 336-346. https://doi.org/10.1097/scs.0b013e3180336047
Mooney, Mark P. ; Losken, H. Wolfgang ; Moursi, Amr ; Shand, Jocelyn M. ; Cooper, Gregory M. ; Curry, Chris ; Ho, Lillian ; Burrows, Anne M. ; Stelnicki, Eric J. ; Losee, Joseph E. ; Opperman, Lynne A. ; Siegel, Michael I. / Postoperative Anti-Tgf-β2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits. In: Journal of Craniofacial Surgery. 2007 ; Vol. 18, No. 2. pp. 336-346.
@article{a8a03c9ff595476d964c70c833c40626,
title = "Postoperative Anti-Tgf-β2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits",
abstract = "Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-β2 (Tgf-β2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-β2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n = 9); 2) suturectomy with nonspecific, control IgG antibody (n = 9); and 3) suturectomy with anti-Tgf-β2 antibody (n = 11). At 10 days of age, a 3 mm × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 μg/suture) or anti-Tgf-β2 (100 μg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P < 0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. Cephalometric analysis revealed significant (P < 0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. These data support the initial hypothesis that interference with Tgf-β2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.",
keywords = "Craniofacial growth, Craniosynostosis, Intracranial volume, Neutralizing antibodies, Rabbits, Tgf-β2",
author = "Mooney, {Mark P.} and Losken, {H. Wolfgang} and Amr Moursi and Shand, {Jocelyn M.} and Cooper, {Gregory M.} and Chris Curry and Lillian Ho and Burrows, {Anne M.} and Stelnicki, {Eric J.} and Losee, {Joseph E.} and Opperman, {Lynne A.} and Siegel, {Michael I.}",
year = "2007",
month = "3",
doi = "10.1097/scs.0b013e3180336047",
language = "English (US)",
volume = "18",
pages = "336--346",
journal = "Journal of Craniofacial Surgery",
issn = "1049-2275",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Postoperative Anti-Tgf-β2 antibody therapy improves intracranial volume and craniofacial growth in craniosynostotic rabbits

AU - Mooney, Mark P.

AU - Losken, H. Wolfgang

AU - Moursi, Amr

AU - Shand, Jocelyn M.

AU - Cooper, Gregory M.

AU - Curry, Chris

AU - Ho, Lillian

AU - Burrows, Anne M.

AU - Stelnicki, Eric J.

AU - Losee, Joseph E.

AU - Opperman, Lynne A.

AU - Siegel, Michael I.

PY - 2007/3

Y1 - 2007/3

N2 - Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-β2 (Tgf-β2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-β2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n = 9); 2) suturectomy with nonspecific, control IgG antibody (n = 9); and 3) suturectomy with anti-Tgf-β2 antibody (n = 11). At 10 days of age, a 3 mm × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 μg/suture) or anti-Tgf-β2 (100 μg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P < 0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. Cephalometric analysis revealed significant (P < 0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. These data support the initial hypothesis that interference with Tgf-β2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.

AB - Postoperative resynostosis and secondary craniofacial growth abnormalities are common sequelae after craniofacial surgery. It has been suggested that an overexpression of transforming growth factor-β2 (Tgf-β2) may be related to craniosynostosis and contribute to postoperative resynostosis. Interference with Tgf-β2 function using neutralizing antibodies may inhibit resynostosis and improve postoperative craniofacial growth; the present study was designed to test this hypothesis. Twenty-nine New Zealand white rabbits with bilateral coronal suture synostosis were used: 1) suturectomy controls (n = 9); 2) suturectomy with nonspecific, control IgG antibody (n = 9); and 3) suturectomy with anti-Tgf-β2 antibody (n = 11). At 10 days of age, a 3 mm × 15-mm coronal suturectomy was performed. The sites in groups 2 and 3 were immediately filled with 0.1 cc of a slow resorbing collagen gel mixed with either IgG (100 μg/suture) or anti-Tgf-β2 (100 μg/suture). Three-dimensional computed tomography scan reconstructions of the skulls and cephalographs were obtained at 10, 25, 42, and 84 days of age. Computed tomography scan data revealed patent suturectomy sites and significantly (P < 0.05) greater intracranial volumes by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. Cephalometric analysis revealed significant (P < 0.05) differences in craniofacial, cranial vault, and cranial base growth by 84 days of age in rabbits treated with anti-Tgf-β2 compared with controls. These data support the initial hypothesis that interference with Tgf-β2 function inhibited postoperative resynostosis and improved cranial vault growth in this rabbit model. Thus, this biologically based therapy may be a potential surgical adjunct in the treatment of infants with craniosynostosis.

KW - Craniofacial growth

KW - Craniosynostosis

KW - Intracranial volume

KW - Neutralizing antibodies

KW - Rabbits

KW - Tgf-β2

UR - http://www.scopus.com/inward/record.url?scp=34247139773&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34247139773&partnerID=8YFLogxK

U2 - 10.1097/scs.0b013e3180336047

DO - 10.1097/scs.0b013e3180336047

M3 - Article

C2 - 17414283

AN - SCOPUS:34247139773

VL - 18

SP - 336

EP - 346

JO - Journal of Craniofacial Surgery

JF - Journal of Craniofacial Surgery

SN - 1049-2275

IS - 2

ER -