Ex vivo Noggin gene therapy inhibits bone formation in a mouse model of postoperative resynostosis.

BACKGROUND

Resynostosis following surgical correction of primary craniosynostosis necessitates further surgical intervention, thereby increasing morbidity and mortality. Bone morphogenetic proteins are known to be expressed during normal bone healing. This study tested the hypothesis that treatment of suturectomy sites with Noggin, an extracellular antagonist of bone morphogenetic proteins, would inhibit postoperative resynostosis in a mouse suturectomy model.

METHODS

Healing of small interfrontal suturectomies was assessed in three groups of mice using radiographic, micro-computed tomographic, and histologic analyses. The groups were as follows: group 1, no treatment (n = 36); group 2, green fluorescent protein (GFP)-labeled cells in a collagen scaffold (n = 36); and group 3, Noggin/GFP-expressing cells in a collagen scaffold (n = 36).

RESULTS

Radiographic analysis of defect area showed that Noggin-treated suturectomy sites were significantly larger than untreated sites 4 and 8 weeks postoperatively (p < 0.05). Analysis of defect volume showed that Noggin-treated defects were significantly larger than untreated defects at all time points after surgery. The GFP-treated defects demonstrated some inhibition of bone formation, but this inhibition was not significant compared with untreated controls 12 weeks after surgery.

CONCLUSIONS

These findings suggest that Noggin is an effective inhibitor of bone formation within small suturectomy sites and that Noggin may be useful in avoiding postoperative resynostosis. Noggin treatment may be useful as an adjunct to traditional surgical intervention for the treatment of children with craniosynostosis.