Changes in the protein expression of hedgehog and patched-1 in perisutural tissues induced by cranial distraction.

Abstract

With the modern emphasis on minimally invasive therapies, the concept of distraction is being applied in the treatment of craniosynostosis. Although specific genetic mutations have been identified in craniosynostotic patients, changes in the gene expression induced by cranial distraction have not yet been explored. The effects of cranial distraction on hedgehog and patched-1 expression were evaluated in a rabbit model for craniosynostosis. Rabbits (n = 8) were divided into four groups: affected rabbits, wild-type rabbits, affected rabbits subject to cranial distraction, and wild-type rabbits subject to distraction. Perisutural tissue was examined using immunohistochemistry in four areas: suture, endosteum, periosteum, and osteocytes, for the expression of Indian hedgehog, sonic hedgehog, and desert hedgehog and their receptor, patched-1. Two experimental groups were compared: (1) wild-type before distraction to wild-type after distraction, and (2) synostotic before distraction to synostotic after distraction. Distraction produced several variable and interesting changes in hedgehog protein presence. In wild-type rabbits, the predominant effect was a mild decrease in Indian hedgehog levels. Sonic and desert hedgehog and patched-1 protein levels were unchanged. In synostotic rabbits, the predominant effect of distraction was to decrease Indian hedgehog, sonic hedgehog, and patched-1 protein levels. This was especially true in the periosteum and endosteum. Cranial distraction of normal and affected rabbits differentially changed both the expression levels and patterns of the hedgehog and patched-1 proteins in the cranial tissues examined. These results suggest that molecular and genetic parameters of distraction and bone response may be different in craniosynostotic individuals, which may influence treatment protocols in these patients.