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Detection of Osteoprotegerin and TNF-alpha mRNA in Ankylotic Stapes Footplates in Connection With Measles Virus Positivity

Authors

  • Tamás Karosi MD, PhD,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
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  • István Jókay MD, PhD,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
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  • József Kónya MD, PhD,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
    2. Department of Medical Microbiology, University Medical School of Debrecen, Debrecen, Hungary
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  • László Z. Szabó MD, PhD,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
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  • József Pytel MD, PhD,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
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  • József Jóri MD, PhD,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
    2. Department of Otolaryngology Head & Neck Surgery, University Medical School of Szeged, Szeged, Hungary.
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  • Anita Szalmás,

    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
    2. Department of Medical Microbiology, University Medical School of Debrecen, Debrecen, Hungary
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  • István Sziklai MD, PhD, DSc

    Corresponding author
    1. Department of Otolaryngology Head & Neck Surgery, University Medical School of Debrecen, Debrecen, Hungary
    2. Department of Otorhinolaryngology, National Health Center, Budapest, Hungary
    • Istvan Sziklai, MD, PhD, DSc, University Medical School of Debrecen, Department of Otolaryngology Head & Neck Surgery, Debrecen, Hungary, H-4012, Nagyerdei Krt. 98., Debrecen, Hungary.
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  • This work was generously supported by grants from Hungarian Scientific Research Fund (OTKA K63743, OTKA F035251, ETT 010/2001, and ETT 415/2003).

Abstract

Hypothesis: Otosclerosis is a bone remodeling disorder of the otic capsule causing conductive and sensorineural hearing loss. Persistent measles virus infection of the temporal bone with increased tumor necrosis factor (TNF)-alpha and decreased osteoprotegerin mRNA expression is supposed to be the main etiologic factor in otosclerosis.

Background: Determinants of measles virus infection and reactive inflammation were studied in otosclerosis. The presence of measles virus was shown in otosclerotic patients by reverse transcriptase-polymerase chain reaction (RT-PCR) amplification of the viral RNA. No report is available, however, about the role and interactions of bone-specific cytokines in otosclerosis.

Methods: Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients. Measles virus nucleoprotein RNA was amplified by seminested RT-PCR. TNF-alpha and osteoprotegerin mRNA coexpression was detected by RT-PCR in otosclerotic bone and was correlated to measles virus positivity.

Results: Among 154 clinically stapes fixation otosclerotic patients, 99 stapedes contained measles virus RNA. TNF-alpha mRNA was detectable in 88 virus-positive and in 6 virus-negative stapes footplates. Osteoprotegerin mRNA expression was significantly lower in the TNF-alpha-positive specimens (P < .0001) that was independent from virus positivity.

Conclusion: Detection of TNF-alpha mRNA demonstrates activated osteoclast functions and inflammatory pathways in otosclerotic stapes footplates associated with measles virus presence. Increased expression of TNF-alpha and its action on RANK production inhibits the protective functions of osteoprotegerin on normal bone turnover in the otic capsule.

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