Conclusion: This study is the first to establish that bone morphogenetic protein 5 (BMP5) plays a role in the pathogenesis of otosclerosis. These results confirm that elevated expression levels of BMPs, members of the transforming growth factor (TGF)-β superfamily, contribute to the pathologically increased bone turnover in early, active stages of otosclerosis. Objectives: Otosclerosis is a complex bone remodeling disorder of the otic capsule, which might be characterized by increased expression of different types of BMPs. TGF-β and BMP are both members of the TGF-β superfamily and play a critical role in bone resorption and new bone formation. It has been suggested that BMP and its receptors may be involved in the pathologically increased bone turnover observed in otosclerosis. Methods: Fifty-one otosclerotic and 16 non-otosclerotic ankylotic stapes footplates were histologically analyzed: conventional hematoxylin-eosin staining and BMP2, 4, 5, and 7specific immunofluorescent assays were performed. Cortical bone fragments (n 35) and incus specimens (n 6) were used as negative controls. Results: Active otosclerosis (n 39) was characterized by increased expression of BMP2, 4, 5, and 7. Inactive cases of otosclerosis (n 12) were characterized by negative immunoreaction for BMPs. Non-otosclerotic stapes specimens (n 16) and negative controls (n 41) showed negligible BMP expression. The BMP expression pattern showed a strong correlation with the histological activity of otosclerosis.
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