Rescue of premature coronal suture fusion with TGF-β2 neutralizing antibody in rabbits with delayed-onset synostosis

Mark P. Mooney; Jocelyn M. Shand; Anne Burrows; Timothy D. Smith; John F. Caccamese.; Gregory M. Cooper; James J. Cray.; James Gilbert; Bernard J. Costello; Joseph E. Losee; Amr M. Moursi; Michael I. Siegel

doi:10.1597/16-065

Rescue of premature coronal suture fusion with TGF-β2 neutralizing antibody in rabbits with delayed-onset synostosis

Mark P. Mooney, Jocelyn M. Shand, Anne Burrows, Timothy D. Smith, John F. Caccamese., Gregory M. Cooper, James J. Cray., James Gilbert, Bernard J. Costello, Joseph E. Losee, Amr M. Moursi, Michael I. Siegel

Pediatric Dentistry

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	844-855
Number of pages	12
Journal	Cleft Palate-Craniofacial Journal
Volume	55
Issue number	6
DOIs	https://doi.org/10.1597/16-065
State	Published - 2018

Keywords

Coronal suture
Craniofacial growth
Craniosynostosis
Neutralizing antibodies
Rabbits
Tgf-β2

ASJC Scopus subject areas

Oral Surgery
Otorhinolaryngology

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10.1597/16-065

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Mooney, M. P., Shand, J. M., Burrows, A., Smith, T. D., Caccamese., J. F., Cooper, G. M., Cray., J. J., Gilbert, J., Costello, B. J., Losee, J. E., Moursi, A. M., & Siegel, M. I. (2018). Rescue of premature coronal suture fusion with TGF-β2 neutralizing antibody in rabbits with delayed-onset synostosis. Cleft Palate-Craniofacial Journal, 55(6), 844-855. https://doi.org/10.1597/16-065

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title = "Rescue of premature coronal suture fusion with TGF-β2 neutralizing antibody in rabbits with delayed-onset synostosis",

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.",

keywords = "Coronal suture, Craniofacial growth, Craniosynostosis, Neutralizing antibodies, Rabbits, Tgf-β2",

author = "Mooney, {Mark P.} and Shand, {Jocelyn M.} and Anne Burrows and Smith, {Timothy D.} and Caccamese., {John F.} and Cooper, {Gregory M.} and Cray., {James J.} and James Gilbert and Costello, {Bernard J.} and Losee, {Joseph E.} and Moursi, {Amr M.} and Siegel, {Michael I.}",

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year = "2018",

doi = "10.1597/16-065",

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pages = "844--855",

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T1 - Rescue of premature coronal suture fusion with TGF-β2 neutralizing antibody in rabbits with delayed-onset synostosis

AU - Mooney, Mark P.

AU - Shand, Jocelyn M.

AU - Burrows, Anne

AU - Smith, Timothy D.

AU - Caccamese., John F.

AU - Cooper, Gregory M.

AU - Cray., James J.

AU - Gilbert, James

AU - Costello, Bernard J.

AU - Losee, Joseph E.

AU - Moursi, Amr M.

AU - Siegel, Michael I.

PY - 2018

Y1 - 2018

N2 - 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.

AB - 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.

KW - Coronal suture

KW - Craniofacial growth

KW - Craniosynostosis

KW - Neutralizing antibodies

KW - Rabbits

KW - Tgf-β2

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Rescue of premature coronal suture fusion with TGF-β2 neutralizing antibody in rabbits with delayed-onset synostosis

Abstract

Keywords

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