TY - JOUR
T1 - Dynamic Molecular Markers of Otosclerosis in the Human Cochlea
AU - Hodge, Sarah
AU - Lopez, Ivan A.
AU - Cronkite, Alex
AU - House, John
AU - Matsui, Hirooki
AU - Ishiyama, Gail
AU - Ishiyama, Akira
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/4
Y1 - 2024/4
N2 - Objective: To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis. Methods: 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. Results: 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. Conclusions: 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.
AB - Objective: To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis. Methods: 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. Results: 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. Conclusions: 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.
KW - immunofluorescence
KW - immunohistochemistry
KW - otosclerosis
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U2 - 10.1177/00034894231225134
DO - 10.1177/00034894231225134
M3 - Article
C2 - 38197255
AN - SCOPUS:85181702498
SN - 0003-4894
VL - 133
SP - 390
EP - 399
JO - Annals of Otology, Rhinology and Laryngology
JF - Annals of Otology, Rhinology and Laryngology
IS - 4
ER -