Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

Abstract

Cholesteatoma is a nonneoplastic lesion of the middle ear space or mastoid that is histologically characterized by a progressive bone erosion of the ossicles and surrounding bone. Several matrix-degrading enzymes have been implicated as mediators of this bone erosion. Because the novel cysteine proteinase cathepsin K has been shown to play a central role in bone resorption, we examined the expression of this enzyme in tissue specimens of cholesteatoma. Tissue specimens of 9 patients with cholesteatoma were obtained during middle-ear surgery. Expression of cathepsin K mRNA was determined by RT-PCR using specific primers. Immunohistochemical analysis of cathepsin K protein expression in tissue sections was performed by using the streptavidin-alkaline phosphatase technique. Expression of both cathepsin K mRNA and protein was detected in areas affected by cholesteatoma, whereas specimens of nonaffected ear cartilage and surrounding tissue were not positive. In addition, cathepsin K was detected in numerous multinucleated giant cells, particularly osteoclasts at the site of bone degradation. In contrast, keratinized squamous epithelium was negative for cathepsin K. These data demonstrate that the matrix-degrading cysteine proteinase cathepsin K may be involved in bone erosion in cholesteatoma. Strong expression of this collagenolytic enzyme in osteoclasts suggests that these cells are mainly involved in cathepsin K-mediated bone destruction.