Force-induced craniosynostosis in the murine sagittal suture.
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.
Oppenheimer
Adam J
AJ
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.
Rhee
Samuel T
ST
Goldstein
Steven A
SA
Buchman
Steven R
SR
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D015415:Biomarkers / Q000032:analysis; D003393:Cranial Sutures / Q000254:growth & development* / Q000378:metabolism; D003398:Craniosynostoses / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D051379:Mice; D008808:Mice, Inbred CBA; D011312:Pressure; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012886:Skull / Q000254:growth & development / Q000378:metabolism; D013314:Stress, Mechanical; D020858:Tissue and Organ Harvesting
D015415:Biomarkers; D000469:Alkaline Phosphatase