Cranial suture response to stress: expression patterns of Noggin and Runx2.
BACKGROUND
Current theory on normal cranial suture fusion entrusts the dura with the regulatory role. Studies suggest that the dura responds to stress with changes in gene expression. Noggin (bone morphogenetic protein inhibitor) expression is decreased in normal (rat and mouse) cranial suture fusion, but its role in craniosynostosis and the response to stress has not been studied.


METHODS
Posterior frontal (fusing) and sagittal (patent) rat cranial sutures were held static, oscillated, or distracted for 10 days in an organ culture microdistraction device beginning at 5 days of age (n = 30 sutures, or 10 sutures per group). The percentage of fusion equaled the score received for bony closure. Noggin, Runx2, and alkaline phosphatase expression was localized by immunohistochemistry for all groups.


RESULTS
Both the posterior frontal and sagittal sutures demonstrated a significant (p < 0.05) increase in fusion percentage with oscillation relative to the static control. Noggin was not expressed in the fusing posterior frontal suture but was expressed in the normally patent sagittal suture. Conversely, Runx2 was expressed in the posterior frontal suture but not in the sagittal suture. However, when a mechanical stress was applied, both the posterior frontal and sagittal sutures expressed Runx2 but not Noggin, as in the static fusing suture.


CONCLUSIONS
The application of mechanical stress to cranial sutures results in fusion of both the posterior frontal suture and the normally patent sagittal suture. Runx2 is expressed but Noggin is not expressed. Thus, mechanical stress influences sutural fusion and may play a role in craniosynostosis.
Heller
Justin B
JB
Los Angeles, Calif. From the Division of Plastic and Reconstructive Surgery, University of California, Los Angeles.
Gabbay
Joubin S
JS
Wasson
Kristy
K
Mitchell
Scott
S
Heller
Misha M
MM
Zuk
Patricia
P
Bradley
James P
JP
D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis* / Q000235:genetics; D003393:Cranial Sutures; D003398:Craniosynostoses / Q000235:genetics / Q000503:physiopathology*; D004388:Dura Mater / Q000502:physiology; D015870:Gene Expression; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D000099176:Noggin Protein
D002352:Carrier Proteins; D050659:Core Binding Factor Alpha 1 Subunit; D000099176:Noggin Protein; C493717:Runx2 protein, rat