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Force-Induced Craniosynostosis in the Murine Sagittal Suture

Oppenheimer, Adam J., M.D.; Rhee, Samuel T., M.D.; Goldstein, Steven A., Ph.D.; Buchman, Steven R., M.D.

Plastic and Reconstructive Surgery: December 2009 - Volume 124 - Issue 6 - p 1840-1848
doi: 10.1097/PRS.0b013e3181bf806c
EXPERIMENTAL: ORIGINAL ARTICLES
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Background: The cause of nonsyndromic craniosynostosis remains elusive. Although compressive forces have been implicated in premature suture fusion, conclusive evidence of force-induced craniosynostosis is lacking. The purpose of this study was to determine whether cyclical loading of the murine calvaria could induce suture fusion.

Methods: Calvarial coupons from postnatal day-21, B6CBA, wild-type mice (n = 18) were harvested and cultured. A custom appliance capable of delivering controlled, cyclical, compressive loads was applied perpendicular to the sagittal suture within the coupon in vitro. Nine coupons were subjected to 0.3 g of force for 30 minutes each day for a total of 14 days. A control group of nine coupons was clamped in the appliance without loading. Analysis of suture phenotype was performed using alkaline phosphatase and hematoxylin and eosin staining techniques and in situ hybridization analysis using bone sialoprotein.

Results: Control group sagittal sutures—which normally remain patent in mice—showed their customary histologic appearance. In contradistinction, sagittal sutures subjected to cyclic loading showed histologic evidence of premature fusion (craniosynostosis). In addition, alkaline phosphatase activity and bone sialoprotein expression were observed to be increased in the experimental group when compared with matched controls.

Conclusions: An in vitro model of force-induced craniosynostosis has been devised. Premature fusion of the murine sagittal suture was induced with the application of controlled, cyclical, compressive loads. These results implicate abnormal forces in the development of nonsyndromic craniosynostosis, which supports our global hypothesis that epigenetic phenomena play a crucial role in the pathogenesis of craniosynostosis.

Ann Arbor, Mich.; and New York, N.Y.

From the Craniofacial Anomalies Program, Section of Plastic Surgery, Department of Surgery, University of Michigan, and the Craniofacial Surgery Program, Department of Surgery, Weill Cornell Medical College.

Received for publication January 7, 2009; accepted May 29, 2009.

Robert H. Ivy Society Award Winner at the 68th Annual Meeting of the American Society of Plastic and Reconstructive Surgeons, in New Orleans, Louisiana, October 23 through 27, 1999.

Disclosure:The authors have no commercial associations, financial disclosures, or other conflicts of interest to report with regard to this article.

Steven R. Buchman, M.D. Section of Plastic Surgery; Department of Surgery; University of Michigan Health System; 2130 Taubman Center, SPC 5340; 1500 East Medical Center Drive; Ann Arbor, Mich. 48109-5340; sbuchman@med.umich.edu

©2009American Society of Plastic Surgeons