Force-induced craniosynostosis in the murine sagittal suture.

Abstract:

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.

journal_name

Plast Reconstr Surg

authors

Oppenheimer AJ,Rhee ST,Goldstein SA,Buchman SR

doi

10.1097/PRS.0b013e3181bf806c

subject

Has Abstract

pub_date

2009-12-01 00:00:00

pages

1840-1848

issue

6

eissn

0032-1052

issn

1529-4242

pii

00006534-200912000-00014

journal_volume

124

pub_type

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