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Activated osteoclasts with CD51/61 expression in otosclerosis
Tamás Karosi1, István Jókay, József Kónya
1Departments of Otolaryngology-Head and Neck Surgery, University Medical School of Debrecen, Nagyerdei Krt. 98, H-4012 Debrecen, Hungary.
Hypothesis:
Stapes ankylosis is supposed to be a disease with variable histopathology caused by otosclerosis or pseudo-otosclerosis. Persistent measles virus infection of the otic capsule could induce reactivation of quiescent embryonic osteoclasts in otosclerosis.
Background:
Presence of measles virus RNA was demonstrated in the footplates of otosclerotic patients by reverse-transcription polymerase chain reaction (RT-PCR). Histology of active otosclerosis is featured by the presence of numerous osteoclasts with unknown phenotype.
Methods:
Nucleic acid was extracted from stapes footplates of clinically otosclerotic patients (n = 261). Genomic RNA of measles virus was amplified by RT-PCR. Amplification results were correlated to postoperative histologic and CD51/61 specific immunohistologic findings. A parallel alcalic phosphatase activity assessment was performed to evaluate the metabolic activity of osteoclasts in each section.
Results:
Among 261 stapes fixation cases, 175 otosclerotic stapes contained measles virus RNA. Histology for virus negative stapes (n = 86) represented nonotosclerotic, degenerative disorders. Histologically confirmed otosclerosis was featured by the presence of osteoclasts with renewed, embryonic phenotype. In otosclerosis, alcalic phosphatase activity was significantly higher compared with nonotosclerotic stapes ankylosis (P < .001).
Conclusion:
The presence of CD51/61 positive osteoclasts in otosclerotic bone containing viral sequences provides the basis for an inflammatory bone remodeling disorder. Otosclerosis is a disease caused by persistent measles virus infection and reactivation of resting embryonic osteoclasts in the otic capsule.
Insights
Measles virus RNA was detected in 175 of 261 otosclerotic stapes, indicating a link between persistent viral infection and otosclerosis. This suggests otosclerosis is an inflammatory bone disorder caused by measles virus reactivating embryonic osteoclasts.
Area of Science:
- Otolaryngology
- Virology
- Pathology
Background:
- Otosclerosis is characterized by variable histopathology, potentially linked to otosclerosis or pseudo-otosclerosis.
- Measles virus RNA presence in otosclerotic stapes footplates has been previously demonstrated via RT-PCR.
- Active otosclerosis histology shows numerous osteoclasts of an unknown phenotype.
Purpose of the Study:
- To investigate the role of persistent measles virus infection in otosclerosis.
- To correlate measles virus presence with histopathological findings and osteoclast activity in stapes ankylosis.
Main Methods:
- Nucleic acid extraction from 261 stapes footplates of clinically otosclerotic patients.
- Genomic RNA amplification of measles virus using RT-PCR.
- Correlation of RT-PCR results with immunohistologic findings (CD51/61) and alkaline phosphatase activity.
Main Results:
- Measles virus RNA was found in 175 out of 261 otosclerotic stapes.
- Virus-negative stapes exhibited nonotosclerotic degenerative disorders.
- Otosclerosis featured osteoclasts with an embryonic phenotype and significantly higher alkaline phosphatase activity compared to nonotosclerotic cases.
Conclusions:
- The presence of CD51/61 positive osteoclasts and viral sequences in otosclerotic bone supports an inflammatory bone remodeling disorder.
- Otosclerosis is proposed to be caused by persistent measles virus infection, reactivating embryonic osteoclasts in the otic capsule.
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