Identification of target proteins involved in cochlear otosclerosis.

Details

Serval ID
serval:BIB_BC1D3B309689
Type
Article: article from journal or magazin.
Collection
Publications
Title
Identification of target proteins involved in cochlear otosclerosis.
Journal
Otology and Neurotology
Author(s)
Richard C., Doherty J.K., Fayad J.N., Cordero A., Linthicum F.H.
ISSN
1537-4505 (Electronic)
ISSN-L
1531-7129
Publication state
Published
Issued date
2015
Volume
36
Number
5
Pages
923-931
Language
english
Abstract
HYPOTHESIS: Investigation of differential protein expression will provide clues to pathophysiology in otosclerosis.
BACKGROUND: Otosclerosis is a bone remodeling disorder limited to the endochondral layer of the otic capsule within the temporal bone. Some authors have suggested an inflammatory etiology for otosclerosis resulting from persistent measles virus infection involving the otic capsule. Despite numerous genetic studies, implication of candidate genes in the otosclerotic process remains elusive. We employed liquid chromatography-mass spectrometry (LC-MS) analysis on formalin-fixed celloidin-embedded temporal bone tissues for postmortem investigation of otosclerosis.
METHODS: Proteomic analysis was performed using human temporal bones from a patient with severe otosclerosis and a control temporal bone. Sections were dissected under microscopy to remove otosclerotic lesions and normal otic capsule for proteomic analysis. Tandem 2D chromatography mass spectrometry was employed. Data analysis and peptide matching to FASTA human databases was done using SEQUEST and proteome discoverer software.
RESULTS: TGFβ1 was identified in otosclerosis but not in the normal control temporal bone specimen. Aside from TGFβ1, many proteins and predicted cDNA-encoded proteins were observed, with implications in cell death and/or proliferation pathways, suggesting a possible role in otosclerotic bone remodeling. Immunostaining using TGFβ1 monoclonal revealed marked staining of the spongiotic otosclerotic lesions.
CONCLUSIONS: Mechanisms involved in cochlear extension of otosclerosis are still unclear, but the implication of TGFβ1 is supported by the present proteomic data and immunostaining results. The established role of TGFβ1 in the chondrogenesis process supports the theory of a reaction targeting the globulae interossei within the otic capsule.
Keywords
Bone Remodeling/physiology, Chondrogenesis/physiology, Chromatography, Liquid, Cochlea/metabolism, Cochlea/pathology, Humans, Otosclerosis/metabolism, Otosclerosis/pathology, Proteomics, Tandem Mass Spectrometry, Temporal Bone/pathology, Transforming Growth Factor beta1/metabolism
Pubmed
Web of science
Create date
09/02/2016 12:47
Last modification date
20/08/2019 15:30
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