Otosclerosis: disturbed balance between cell survival and apoptosis.
OBJECTIVE
Otosclerosis is an inflammatory bone remodeling disorder of the human otic capsule, which might be characterized by a disturbed balance between cell survival and apoptosis due to an increased expression of inflammatory cytokines, mainly tumor necrosis factor-[alpha] (TNF-[alpha]).


BACKGROUND
Histologic features of otosclerosis have been well described; however, different histopathologic and clinical stages have not been attributed precisely to the molecular biology of the pathologically increased metabolism of bone-forming and bone-resorbing cells.


METHODS
Forty ankylotic stapes footplates (n = 40, males = 17, females = 23) removed by stapedectomy were histologically analyzed by conventional hematoxylin-eosin staining, and hCIAP1/2 (inhibitors of apoptosis) and granzyme-[beta] (apoptosis inducer) specific immunofluorescent assays were performed. Four normal stapes footplates obtained from cadavers with negative otologic history were used as negative controls.


RESULTS
Active otosclerosis (n = 19) was featured by robust expression of apoptosis inhibitor proteins hCIAP1/2 and negligible expression of granzyme-[beta]. Inactive cases of otosclerosis (n = 8) were characterized by inverse reaction: granzyme-[beta] was highly expressed; however, hCIAP1/2 specific immunoreactions were absent. Nonotosclerotic and normal stapes specimens showed no considerable little granzyme-[beta] expression and moderate hCIAP1/2-specific immunoreactions. Expression pattern of apoptosis-associated proteins showed strong correlation with the histologic diagnosis and activity of otosclerosis (Yates-corrected [chi]2 test, p < 0.001).


CONCLUSIONS
Detection of the inversely expressed apoptosis inhibitor and inducer proteins in active and inactive stages of otosclerosis demonstrates pathologic regulation of cell survival and apoptosis. These results may suggest active otosclerosis inactivation by TNF-[alpha] induced apoptosis. Anti-TNF-[alpha] biologics may serve as an option in the medical treatment of active otosclerosis.
Csomor
Péter
P
Medical and Health Science Center, Department of Otolaryngology Head and Neck Surgery, University of Debrecen, Debrecen, Hungary.
Sziklai
István
I
Liktor
Bálint
B
Szabó
László
L
Pytel
József
J
Jóri
József
J
Karosi
Tamás
T
D000328:Adult; D000368:Aged; D000844:Ankylosis / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D015415:Biomarkers; D001862:Bone Resorption / Q000473:pathology; D002470:Cell Survival / Q000502:physiology*; D005260:Female; D005455:Fluorescent Antibody Technique; D053804:Granzymes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010040:Otosclerosis / Q000473:pathology* / Q000601:surgery; D013199:Stapes / Q000473:pathology; D013201:Stapes Surgery; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D051034:Inhibitor of Apoptosis Proteins; D014409:Tumor Necrosis Factor-alpha; D053804:Granzymes