Mechanismofboneresorption inmiddleearcholesteatoma inthe light of H^+ concentration and H^+-sensing Proteins

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Objective:The etiopathology of bone resorption in cholesteatoma is unclear. We studied pH inmiddle ear cholesteatoma tissue and the permeability of the cholesteatoma epithelium in an attempt to elucidate the mechanism of bone resorption in this disease.Methods:Cholesteatoma tissue was collected from patients with primary acquired middle ear cholesteatoma. The pH of the keratin debris of cholesteatoma was measured using a pH meter. The cholesteatoma epithelium was examined under a confocal laser scanning microscope, and under a transmission electron microscope. Expression of filaggrin in the cholesteatoma tissue was explored by fluorescence immunohistochemistry and by quantitative reverse transcription-polymerase chain reaction.Results: The pH of the keratin debris of cholesteatoma was acidic. The pH of the basal layer of the cholesteatoma epithelium was significantly lower than that of the antrum mucosa. Transmission electron microscope showed distinct penetration of lanthanum in the intercellular space of the basal, spinous and granular layers of the cholesteatoma epithelium, but only a small amount of lanthanum in the granular layer in the normal skin. The expression of filaggrin nlRNA was significantly lower in the cholesteatoma tissue than in the normal skin.Conclusions: These results indicate that acid leakage through the cholesteatonla epitheliunl probably participates in the resorption of the underlying bone structure. The increased permeability of the cholesteatoma epitheliunl may be explained by a decrease in filaggrin expression.