RESUMO
OBJECTIVES: To investigate the expression of osteoclast-activating and differentiating factors and to study the occurrence of osteoclast precursor cells and osteoclasts in acquired human cholesteatoma tissue. METHODS: We examined 21 cholesteatoma samples versus 18 normal auditory canal skin specimens for the expression of osteoprotegerin ligand (OPGL), osteoprotegerin (OPG), and macrophage-colony stimulating factor (M-CSF) using reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. Immunohistochemistry and computer-assisted microscopy using markers CD4, CD11a, CD11b, CD14, CD51, CD68, and TRAP obtained the detection of osteoclast cell lineage. RESULTS: An increased expression of the investigated cytokines M-CSF, OPG, and OPGL was demonstrated by immunohistochemistry and RT-PCR in cholesteatoma tissue compared with normal external meatal skin. Several CD4-positive cells exhibited a co-expression for OPGL within the perimatrix of cholesteatoma. The presence of osteoclast precursor cells was confirmed in all samples of cholesteatoma tissue. CONCLUSIONS: This study reveals that the number of osteoclast precursor cells is markedly increased in the perimatrix of cholesteatoma tissue. Our results support a concept described for inflammatory arthritis: the inflammation related to cholesteatoma induces bone resorption by release of OPGL from activated T-cells and triggers osteoclastogenesis. This could be a major target for drugs to inhibit osteoclast formation and bone resorption and may be an adjunct in cholesteatoma management.
