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Rescue of Premature Coronal Suture Fusion with TGF-β2 Neutralizing Antibody in Rabbits with Delayed-Onset Synostosis.

Authors
  • Mooney, Mark P1
  • Shand, Jocelyn M2
  • Burrows, Anne3
  • Smith, Timothy D4
  • Caccamese, John F Jr5
  • Cooper, Gregory M6
  • Cray, James J Jr7
  • Gilbert, James8
  • Costello, Bernard J9
  • Losee, Joseph E10
  • Moursi, Amr M11
  • Siegel, Michael I12
  • 1 Department of Oral Biology, Plastic and Reconstructive Surgery, Orthodontics, and Communication Science and Disorders, Cleft Palate-Craniofacial Center, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 2 Department of Oral and Maxillofacial Surgery, School of Dental Science, University of Melbourne, Melbourne, Australia. , (Australia)
  • 3 Department of Physical Therapy, Rangos School of Health Sciences, Duquesne University, Pittsburgh, Department of Anthropology, University of Pittsburgh, Pennsylvania.
  • 4 School of Physical Therapy, Slippery Rock University, Slippery Rock, Pennsylvania, Department of Anthropology, University of Pittsburgh, Pennsylvania.
  • 5 Department of Oral and Maxillofacial Surgery, University of Maryland, Baltimore, Maryland.
  • 6 Department of Plastic and Reconstructive Surgery, Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 7 Department of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina.
  • 8 Department of Plastic and Reconstructive Surgery, University of Pittsburgh, Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania.
  • 9 Division of Craniofacial and Cleft Surgery, Department of Oral and Maxillofacial Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 10 Pediatric Plastic Surgery, Cleft Palate-Craniofacial Center, Children's Hospital of Pittsburgh, Plastic and Reconstructive Surgery and Pediatrics, University of Pittsburgh, Pittsburgh, Pennsylvania.
  • 11 Department of Pediatric Dentistry, College of Dentistry, New York University, New York, New York.
  • 12 Departments of Anthropology, Orthodontics, and Oral Biology, University of Pittsburgh, Pittsburgh, Pennsylvania.
Type
Published Article
Journal
The Cleft palate-craniofacial journal : official publication of the American Cleft Palate-Craniofacial Association
Publication Date
Jan 01, 2018
Pages
16065–16065
Identifiers
DOI: 10.1597/16-065
PMID: 27505182
Source
Medline
Keywords
License
Unknown

Abstract

Objectives An overexpression of Tgf-β2 leads to calvarial hyperostosis and suture fusion in individuals with craniosynostosis. Inhibition of Tgf-β2 may help rescue fusing sutures and restore normal growth. The present study was designed to test this hypothesis. Design Twenty-eight New Zealand White rabbits with delayed-onset coronal synostosis had radiopaque markers placed on either side of the coronal sutures at 10 days of age. The rabbits were randomly assigned to: (1) sham control rabbits (n = 10), (2) rabbits with control IgG (100 μg/suture) delivered in a collagen vehicle (n = 9), and (3) rabbits with Tgf-β2 neutralizing antibody (100 μg/suture) delivered in a collagen vehicle (n = 9). Longitudinal growth data were collected at 10, 25, 42, and 84 days of age. Sutures were harvested at 84 days of age for histomorphometry. Results Radiographic analysis showed significantly greater ( P < .05) coronal suture marker separation, craniofacial length, cranial vault length, height, shape indices, cranial base length, and more lordotic cranial base angles in rabbits treated with anti-Tgf-β2 antibody than in controls at 42 and 84 days of age. Histologically, rabbits treated with anti-Tgf-β2 antibody at 84 days of age had patent and significantly ( P < .05) wider coronal sutures and greater sutural area compared to controls. Conclusions These data support our hypothesis that antagonism of Tgf-β2 may rescue fusing coronal sutures and facilitate craniofacial growth in this rabbit model. These findings also suggest that cytokine therapy may have clinical significance in infants with progressive postgestational craniosynostosis.

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