Detection of osteoprotegerin and TNF-alpha mRNA in ankylotic staples footplates in connection with measles virus positivity

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. TNFalpha 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 TNFalpha-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.