Osteoclast stimulating and differentiating factors in human cholesteatoma.
OBJECTIVE
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.
Hamzei
Michael
M
Department of Otolaryngology-Head and Neck Surgery, University of Bochum, St. Elisabeth Hospital, Bleichstrasse 15, 44787 Bochum, Germany.
Ventriglia
Giovanni
G
Hagnia
Mitra
M
Antonopolous
Alexandra
A
Bernal-Sprekelsen
Manuel
M
Dazert
Stefan
S
Hildmann
Henning
H
Sudhoff
Holger
H
D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D030161:Avian Proteins; D001862:Bone Resorption; D040881:CD11a Antigen / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology / Q000378:metabolism*; D018424:Cholesteatoma, Middle Ear / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D046508:Culture Techniques; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D017931:DNA Primers / Q000276:immunology; D018076:DNA, Complementary / Q000276:immunology; D005136:Eye Proteins / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000276:immunology; D016173:Macrophage Colony-Stimulating Factor / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D010010:Osteoclasts / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D030161:Avian Proteins; D040881:CD11a Antigen; D015704:CD4 Antigens; D002352:Carrier Proteins; D016207:Cytokines; D017931:DNA Primers; D018076:DNA, Complementary; D005136:Eye Proteins; D006023:Glycoproteins; D039564:Integrin alphaV; D018950:Lipopolysaccharide Receptors; D016173:Macrophage Colony-Stimulating Factor; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human