Tags

Type your tag names separated by a space and hit enter

Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model.
Orthod Craniofac Res 2009; 12(3):254-62OC

Abstract

INTRODUCTION

- The mechanisms underlying craniosynostosis remains unknown. However, mutations in FGFR2 are associated with craniosynostotic syndromes. We previously compared gene expression patterns of patent and synostosing coronal sutures in the nude rat and demonstrated down regulation of Noggin in synostosing sutures. Noggin expression is also suppressed by FGF2 and constitutive FGFR2 signaling [Warren et al. (2003) Nature, vol. 422, pp. 625-9; McMahon et al. (1998) Genes Dev, vol. 12, pp. 1438-52]. Thus, we therefore hypothesized that the addition of rhNoggin to prematurely fusing sutures should prevent synostosis. MATERIALS AND

METHODS -

Cohorts of nude rats were subjected to: 1) surgical elevation of the coronal suture (shams); 2) surgical elevation and placement of normal or FGFR2 mutant human osteoblasts onto the underlying dura (xenotransplants); or 3) xenotransplantation with co-application of heparin acrylic beads soaked with recombinant human (rh) Noggin. Eleven days post-surgery the sutures were harvested, stained, and histologically examined.

RESULTS -

Animals that received control osteoblasts, sham surgery, or no surgery demonstrated normal skull growth and coronal suture histology, whereas animals transplanted only with FGFR2 mutant osteoblasts showed evidence of bridging synostosis on the calvarial dural surface. Sutures treated with FGFR2 mutant osteoblasts and rhNoggin remained patent.

CONCLUSION -

The chimeric nude rate model is a viable model of craniosynostosis. FGFR2 mutations in osteoblasts induce bridging osteosynthesis demonstrating one of the mechanisms for premature suture fusion. Topical application of rhNoggin protein prevents craniosynostosis in the weanling nude rat xenotransplantation model of syndromic craniosynostosis.

Authors+Show Affiliations

Center for Genomic Sciences, Allegheny Singer Research Institute, Pittsburgh, PA 15212, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19627528

Citation

Shen, K, et al. "Medical Treatment of Craniosynostosis: Recombinant Noggin Inhibits Coronal Suture Closure in the Rat Craniosynostosis Model." Orthodontics & Craniofacial Research, vol. 12, no. 3, 2009, pp. 254-62.
Shen K, Krakora SM, Cunningham M, et al. Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model. Orthod Craniofac Res. 2009;12(3):254-62.
Shen, K., Krakora, S. M., Cunningham, M., Singh, M., Wang, X., Hu, F. Z., ... Ehrlich, G. D. (2009). Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model. Orthodontics & Craniofacial Research, 12(3), pp. 254-62. doi:10.1111/j.1601-6343.2009.01460.x.
Shen K, et al. Medical Treatment of Craniosynostosis: Recombinant Noggin Inhibits Coronal Suture Closure in the Rat Craniosynostosis Model. Orthod Craniofac Res. 2009;12(3):254-62. PubMed PMID: 19627528.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Medical treatment of craniosynostosis: recombinant Noggin inhibits coronal suture closure in the rat craniosynostosis model. AU - Shen,K, AU - Krakora,S M, AU - Cunningham,M, AU - Singh,M, AU - Wang,X, AU - Hu,F Z, AU - Post,J C, AU - Ehrlich,G D, PY - 2009/7/25/entrez PY - 2009/7/25/pubmed PY - 2009/10/30/medline SP - 254 EP - 62 JF - Orthodontics & craniofacial research JO - Orthod Craniofac Res VL - 12 IS - 3 N2 - INTRODUCTION - The mechanisms underlying craniosynostosis remains unknown. However, mutations in FGFR2 are associated with craniosynostotic syndromes. We previously compared gene expression patterns of patent and synostosing coronal sutures in the nude rat and demonstrated down regulation of Noggin in synostosing sutures. Noggin expression is also suppressed by FGF2 and constitutive FGFR2 signaling [Warren et al. (2003) Nature, vol. 422, pp. 625-9; McMahon et al. (1998) Genes Dev, vol. 12, pp. 1438-52]. Thus, we therefore hypothesized that the addition of rhNoggin to prematurely fusing sutures should prevent synostosis. MATERIALS AND METHODS - Cohorts of nude rats were subjected to: 1) surgical elevation of the coronal suture (shams); 2) surgical elevation and placement of normal or FGFR2 mutant human osteoblasts onto the underlying dura (xenotransplants); or 3) xenotransplantation with co-application of heparin acrylic beads soaked with recombinant human (rh) Noggin. Eleven days post-surgery the sutures were harvested, stained, and histologically examined. RESULTS - Animals that received control osteoblasts, sham surgery, or no surgery demonstrated normal skull growth and coronal suture histology, whereas animals transplanted only with FGFR2 mutant osteoblasts showed evidence of bridging synostosis on the calvarial dural surface. Sutures treated with FGFR2 mutant osteoblasts and rhNoggin remained patent. CONCLUSION - The chimeric nude rate model is a viable model of craniosynostosis. FGFR2 mutations in osteoblasts induce bridging osteosynthesis demonstrating one of the mechanisms for premature suture fusion. Topical application of rhNoggin protein prevents craniosynostosis in the weanling nude rat xenotransplantation model of syndromic craniosynostosis. SN - 1601-6343 UR - https://www.unboundmedicine.com/medline/citation/19627528/Medical_treatment_of_craniosynostosis:_recombinant_Noggin_inhibits_coronal_suture_closure_in_the_rat_craniosynostosis_model_ L2 - https://doi.org/10.1111/j.1601-6343.2009.01460.x DB - PRIME DP - Unbound Medicine ER -