Objective: To investigate the role of key proteins in the complex pathogenesis of otosclerosis in human temporal bones
Background: Molecular biological proteomic studies have suggested key proteins involved in bony remodeling in otosclerosis. The present study investigates the expression of some of these key proteins: transforming growth factor beta-1 (TGF beta-1), ubiquitin, nidogen-1, collagen-X, and bone sialoprotein (BSP) using immunohistochemistry techniques on celloidin embedded sections of the inner ear from patients with otosclerosis.
Methods: Archival celloidin formalin-fixed 20-micron thick sections from 7 patients diagnosed with otosclerosis were studied. Sections in the mid-modiolar region were immunoreacted with rabbit polyclonal antibodies against nidogen-1, collagen X, BSP, and monoclonal antibodies against TGF beta-1 and ubiquitin. Digital images were acquired using a highresolution light and laser confocal microscope.
Results: TGF beta-1, ubiquitin, nidogen-1, and collagen-X were expressed in the otospongiotic region, and to lesser extent, in the otosclerotic region, the latter previously believed to be inactive. BSP, meanwhile, was present in the extracellular bone matrix. TGF beta-1 was specifically localized to the perivascular bone within the otospongiotic region. Ubiquitin distribution localized to both the otosclerotic and otospongiotic foci, and within the membranous labyrinth. There was a basal level of expression of these markers in the normal hearing specimens with increasingly more expression as hearing loss progressed.
Conclusions: These proteins identified and described using immunohistochemistry may play an important role in the pathogenesis of otosclerosis. Results support an active bone remodeling process, particularly in the otospongiotic foci suggesting these proteins may be targets for future therapeutic interventions.
Professional Practice Gap & Educational Need: The definitive biochemical changes involved in otosclerosis are widely unknown. Identifying and characterizing molecular markers is a crucial component to better understanding this disease process.
Learning Objective: To describe the role of key biochemical markers in the complex pathogenesis of otosclerosis
Desired Result: Identifying the presence and distribution of key proteins can help elucidate molecular processes and identify possible targets for future therapeutics.