Dynamic Molecular Markers of Otosclerosis in the Human Cochlea

To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis.

Archival celloidin formalin-fixed 20-micron thick histologic sections from 7 patients diagnosed with otosclerosis were studied and compared to controls. Sections in the mid-modiolar region were immunoreacted with rabbit polyclonal antibodies against nidogen-1, β2-laminin, collagen-IX, BSP, and monoclonal antibodies against TGF β-1 and ubiquitin. Digital images were acquired using a high-resolution light and laser confocal microscope.

Nidogen-1, BSP, and collagen-IX were expressed in the otospongiotic regions, and to lesser extent, in the otosclerotic regions, the latter previously believed to be inactive. β2-laminin and ubiquitin were uniformly expressed in both otospongiotic and otosclerotic regions. There was a basal level of expression of all of these markers in the normal hearing and sensorineural hearing loss specimens utilized as control. TGF β -1, however, though present in the otosclerosis bones, was absent in the normal hearing and sensorineural hearing loss controls.

Our results propose that the activity and function of TGF-1 may play a key role in the development and pathogenesis of otosclerosis. Further studies utilizing a higher number of temporal bone specimens will be helpful for future analysis and to help decipher its role as a potential target in therapeutic interventions.