Noggin inhibits postoperative resynostosis in craniosynostotic rabbits

Gregory M. Cooper, Chris Curry, Timothy E. Barbano, Anne M. Burrows, Lisa Vecchione, John F. Caccamese, Craig S. Norbutt, Bernard J. Costello, Joseph E. Losee, Amr Moursi, Johnny Huard, Mark P. Mooney

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1046-1054
Number of pages9
JournalJournal of Bone and Mineral Research
Volume22
Issue number7
DOIs
StatePublished - Jul 2007

Fingerprint

Craniosynostoses
Sutures
Bone Morphogenetic Proteins
Rabbits
Osteogenesis
Collagen
Gels
Cranial Sutures
Synostosis
Skull Base
Brain
Wound Healing
Morbidity
Bone and Bones
Mortality
Therapeutics
Growth

Keywords

  • Bone healing
  • Craniosynostosis
  • Noggin
  • Postoperative resynostosis
  • Rabbit model

ASJC Scopus subject areas

  • Surgery

Cite this

Cooper, G. M., Curry, C., Barbano, T. E., Burrows, A. M., Vecchione, L., Caccamese, J. F., ... Mooney, M. P. (2007). Noggin inhibits postoperative resynostosis in craniosynostotic rabbits. Journal of Bone and Mineral Research, 22(7), 1046-1054. https://doi.org/10.1359/jbmr.070410

Noggin inhibits postoperative resynostosis in craniosynostotic rabbits. / Cooper, Gregory M.; Curry, Chris; Barbano, Timothy E.; Burrows, Anne M.; Vecchione, Lisa; Caccamese, John F.; Norbutt, Craig S.; Costello, Bernard J.; Losee, Joseph E.; Moursi, Amr; Huard, Johnny; Mooney, Mark P.

In: Journal of Bone and Mineral Research, Vol. 22, No. 7, 07.2007, p. 1046-1054.

Research output: Contribution to journalArticle

Cooper, GM, Curry, C, Barbano, TE, Burrows, AM, Vecchione, L, Caccamese, JF, Norbutt, CS, Costello, BJ, Losee, JE, Moursi, A, Huard, J & Mooney, MP 2007, 'Noggin inhibits postoperative resynostosis in craniosynostotic rabbits', Journal of Bone and Mineral Research, vol. 22, no. 7, pp. 1046-1054. https://doi.org/10.1359/jbmr.070410
Cooper GM, Curry C, Barbano TE, Burrows AM, Vecchione L, Caccamese JF et al. Noggin inhibits postoperative resynostosis in craniosynostotic rabbits. Journal of Bone and Mineral Research. 2007 Jul;22(7):1046-1054. https://doi.org/10.1359/jbmr.070410
Cooper, Gregory M. ; Curry, Chris ; Barbano, Timothy E. ; Burrows, Anne M. ; Vecchione, Lisa ; Caccamese, John F. ; Norbutt, Craig S. ; Costello, Bernard J. ; Losee, Joseph E. ; Moursi, Amr ; Huard, Johnny ; Mooney, Mark P. / Noggin inhibits postoperative resynostosis in craniosynostotic rabbits. In: Journal of Bone and Mineral Research. 2007 ; Vol. 22, No. 7. pp. 1046-1054.
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