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

Huard, J and Cooper, GM and Usas, A and Olshanski, A and Mooney, MP and Losee, JE (2009) Ex vivo noggin gene therapy inhibits bone formation in a mouse model of postoperative resynostosis. Plastic and Reconstructive Surgery, 123 (SUPPL.). ISSN 0032-1052

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Abstract

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. © 2009 by the American Society of Plastic Surgeons.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Huard, J
Cooper, GMgmc8@pitt.eduGMC8
Usas, A
Olshanski, A
Mooney, MPmpm4@pitt.eduMPM4
Losee, JEjel35@pitt.eduJEL35
Centers: Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date: 18 September 2009
Date Type: Publication
Journal or Publication Title: Plastic and Reconstructive Surgery
Volume: 123
Number: SUPPL.
DOI or Unique Handle: 10.1097/prs.0b013e318191c05b
Schools and Programs: Dietrich School of Arts and Sciences > Anthropology
School of Dental Medicine > Dental Science
School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
School of Medicine > Pathology
School of Medicine > Pediatrics
School of Medicine > Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 0032-1052
MeSH Headings: Animals; Bone Morphogenetic Proteins--antagonists & inhibitors; Bone Regeneration--drug effects; Carrier Proteins--pharmacology; Cells, Cultured; Craniosynostoses--surgery; Disease Models, Animal; Genetic Therapy; Growth Inhibitors--pharmacology; Male; Mice; Mice, Inbred C57BL; Models, Animal; Osteogenesis--drug effects; Reconstructive Surgical Procedures--adverse effects; Synostosis--etiology; Synostosis--prevention & control; Wound Healing--drug effects
PubMed ID: 19182668
Date Deposited: 09 Apr 2014 16:39
Last Modified: 02 Apr 2020 13:58
URI: http://d-scholarship.pitt.edu/id/eprint/21046

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