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Noggin inhibits postoperative resynostosis in craniosynostotic rabbits

Cooper, GM and Curry, C and Barbano, TE and Burrows, AM and Vecchione, L and Caccamese, JF and Norbutt, CS and Costello, BJ and Losee, JE and Moursi, AM and Huard, J and Mooney, MP (2007) Noggin inhibits postoperative resynostosis in craniosynostotic rabbits. Journal of Bone and Mineral Research, 22 (7). 1046 - 1054. ISSN 0884-0431

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Abstract

Inhibition of bone formation after surgery to correct craniosynostosis would alleviate the need for secondary surgeries and decrease morbidity and mortality. This study used a single dose of Noggin protein to prevent resynostosis and improve postoperative outcomes in a rabbit model of craniosynostosis. Introduction: Craniosynostosis is defined as the premature fusion of one or more of the cranial sutures, which causes secondary deformations of the cranial vault, cranial base, and brain. Current surgical intervention involves extirpation of the fused suture to allow unrestricted brain growth. However, resynostosis of the extirpated regions often occurs. Several bone morphogenetic proteins (BMPs), well-described inducers of ossification, are involved in bone healing. This study tested the hypothesis that a postoperative treatment with Noggin, an extracellular BMP inhibitor, can inhibit resynostosis in a rabbit model of human familial nonsyndromic craniosynostosis. Materials and Methods: Thirty-one New Zealand white rabbits with bilateral coronal suture synostosis were divided into three groups: (1) suturectomy controls (n = 13); (2) suturectomy with BSA in a slow-resorbing collagen vehicle, (n = 8); and (3) suturectomy with Noggin in a slow-resorbing collagen vehicle (n = 10). 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 BSA-loaded gel or Noggin-loaded gel, respectively. Serial 3D-CT scan reconstructions of the defects and standard radiographs were obtained at 10, 25, 42, and 84 days of age, and the sutures were harvested for histological analysis. Results: Radiographic analysis revealed that Noggin-treated animals had significantly greater coronal suture marker separation by 25 days and significantly greater craniofacial length at 84 days of age compared with controls. 3D-CT analysis revealed that Noggin treatment led to significantly greater defect areas through 84 days and to increased intracranial volumes at 84 days of age compared with other groups. Histological analysis supported CT data, showing that the untreated and BSA-treated groups had significant healing of the suturectomy site, whereas the Noggin-treated group had incomplete wound healing. Conclusions: These data support our hypothesis that inhibition of BMP activity using Noggin may prevent postoperative resynostosis in this rabbit model. These findings also suggest that Noggin therapy may have potential clinical use to prevent postoperative resynostosis in infants with craniosynostosis. © 2007 American Society for Bone and Mineral Research.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Cooper, GMgmc8@pitt.eduGMC8
Curry, C
Barbano, TE
Burrows, AM
Vecchione, L
Caccamese, JF
Norbutt, CS
Costello, BJbjc1@pitt.eduBJC1
Losee, JEjel35@pitt.eduJEL35
Moursi, AM
Huard, J
Mooney, MPmpm4@pitt.eduMPM4
Date: 1 July 2007
Date Type: Publication
Journal or Publication Title: Journal of Bone and Mineral Research
Volume: 22
Number: 7
Page Range: 1046 - 1054
DOI or Unique Handle: 10.1359/jbmr.070410
Schools and Programs: Dietrich School of Arts and Sciences > Anthropology
School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 0884-0431
MeSH Headings: Animals; Body Weight--drug effects; Carrier Proteins--pharmacology; Cephalometry; Craniosynostoses--chemically induced; Craniosynostoses--prevention & control; Disease Models, Animal; Postoperative Period; Rabbits; Recurrence; Tomography, X-Ray Computed
PubMed ID: 17437358
Date Deposited: 09 Jun 2014 14:44
Last Modified: 02 Feb 2019 14:55
URI: http://d-scholarship.pitt.edu/id/eprint/21668

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