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


CONCLUSIONS
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.
Karosi
Tamás
T
Department of Otolaryngology/Head & Neck Surgery, University Medical School of Debrecen, Nagyerdei Krt. 98, H-4012 Debrecen, Hungary.
Jókay
István
I
Kónya
József
J
Szabó
László Z
LZ
Pytel
József
J
Jóri
József
J
Szalmás
Anita
A
Sziklai
István
I
D000328:Adult; D002352:Carrier Proteins / Q000502:physiology; D005260:Female; D006023:Glycoproteins / Q000032:analysis* / Q000235:genetics; D006801:Humans; D008297:Male; D008457:Measles / Q000150:complications*; D008459:Measles virus / Q000302:isolation & purification*; D008562:Membrane Glycoproteins / Q000502:physiology; D008875:Middle Aged; D053244:Osteoprotegerin; D010040:Otosclerosis / Q000209:etiology* / Q000378:metabolism; D053245:RANK Ligand; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000032:analysis; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013199:Stapes / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis* / Q000235:genetics
D002352:Carrier Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D012367:RNA, Viral; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha