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.
Cooper
Gregory M
GM
Pittsburgh, Pa. From the Departments of Surgery (Division of Pediatric Plastic Surgery), Oral Biology, Oral Medicine, Pathology, Anthropology, Orthodontics, Orthopedic Surgery, Molecular Genetics and Biochemistry, and Bioengineering, University of Pittsburgh; and the Stem Cell Research Center, Children's Hospital of Pittsburgh.
Usas
Arvydas
A
Olshanski
Anne
A
Mooney
Mark P
MP
Losee
Joseph E
JE
Huard
Johnny
J
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D001861:Bone Regeneration / Q000187:drug effects*; D002352:Carrier Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D003398:Craniosynostoses / Q000601:surgery; D004195:Disease Models, Animal; D015316:Genetic Therapy; D006131:Growth Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010012:Osteogenesis / Q000187:drug effects*; D019651:Plastic Surgery Procedures / Q000009:adverse effects; D013580:Synostosis / Q000209:etiology / Q000517:prevention & control*; D014945:Wound Healing / Q000187:drug effects; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D006131:Growth Inhibitors; D000099176:Noggin Protein