title: Identification of target proteins involved in cochlear otosclerosis.
abstract: OBJECTIVE
  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.
authors.affiliation: *Otorhinolaryngology Department, Hôpital Nord-Ouest, Villefranche-sur-Saône, France; †Shohet Ear Associates Medical Group, Seal Beach, California; ‡House Clinic, Los Angeles, California; §House Temporal Bone Laboratory, University of California, Los Angeles, California, U.S.A.
authors.forename: Céline
authors.initials: C
authors.lastname: Richard
authors.forename: Joni K
authors.initials: JK
authors.lastname: Doherty
authors.forename: Jose N
authors.initials: JN
authors.lastname: Fayad
authors.forename: Ana
authors.initials: A
authors.lastname: Cordero
authors.forename: Fred H
authors.initials: FH
authors.lastname: Linthicum
mesh_terms: D016723:Bone Remodeling / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology; D002853:Chromatography, Liquid; D003051:Cochlea / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D010040:Otosclerosis / Q000378:metabolism* / Q000473:pathology; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D013701:Temporal Bone / Q000473:pathology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1