Comprehensive cornified envelope protein profile of odontogenic keratocysts clarifies the characteristics of non-keratinized oral epithelium.

Abstract

Odontogenic keratocysts constitute 10%-20% of odontogenic cysts and exhibit a distinctive corrugated parakeratinized lining epithelium. Considering that cornified envelope formation is an important phenomenon during keratinocyte differentiation, this study aimed to clarify the characteristics of cornified envelope formation in odontogenic keratocysts. We investigated the cellular distribution of cornified envelope-related proteins (transglutaminases and their substrates), as well as the upstream regulatory protein c-Fos, by immunohistochemical analysis of the lining epithelium of 20 odontogenic keratocysts. We examined the corresponding mRNA levels by quantitative polymerase chain reaction. Ten dentigerous cysts served as control non-keratinized cysts. The distributions of transglutaminase and their substrates except loricrin and small protein-rich protein 1a significantly differed between odontogenic keratocysts and dentigerous cysts. There was no significant difference in c-Fos expression between odontogenic keratocysts and dentigerous cysts. The mRNA levels of transglutaminases and their substrates were significantly higher in odontogenic keratocysts than in dentigerous cysts. However, c-Fos mRNA levels did not significantly differ between groups. Surprisingly, the overall appearance of cornified envelope-related proteins of odontogenic keratocysts was consistent with the characteristics of non-keratinized oral mucosa identified in previous studies. These findings indicate that the contribution of cornified envelope-related molecules in odontogenic keratocysts is similar to that in non-keratinized oral epithelium, rather than keratinized oral epithelium, suggesting that odontogenic keratocysts are not genuine keratinized cysts. The upregulation of cornified envelope-related genes in odontogenic epithelium could be an important pathognomonic event during odontogenic keratocyst development.