ArticleJournal of the Association for Research in Otolaryngology : JARO2019
Osteoclasts Modulate Bone Erosion in Cholesteatoma via RANKL Signaling.
Article in Journal of the Association for Research in Otolaryngology : JARO, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Expression and Regulatory Mechanisms of MicroRNA in Cholesteatoma: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.Current medicinal chemistry · 2026Review
- Emerging Paradigms in Cholesteatoma: From a Traditional Approach to Personalized Therapy.International journal of molecular sciences · 2025Review
- ROS-responsive adaptive injectable hydrogel promoting inflammatory mastoid bone repair through efficient sterilization and regulating oxidative stress and macrophage phenotype.Materials today. Bio · 2025Article
- Cholesteatoma Severely Impacts the Integrity and Bone Material Quality of the Incus.Calcified tissue international · 2023Article
- Single-cell transcriptomics of human cholesteatoma identifies an activin A-producing osteoclastogenic fibroblast subset inducing bone destruction.Nature communications · 2023Article
- Whole exome sequencing study identifies candidate loss of function variants and locus heterogeneity in familial cholesteatoma.PloS one · 2023Article
- Review of potential medical treatments for middle ear cholesteatoma.Cell communication and signaling : CCS · 2022Review
- Endotyping of Cholesteatoma: Which Molecular Biomarkers? A Systematic Review.Journal of personalized medicine · 2022Review
- The Relationship between the M1/M2 Macrophage Polarization and the Degree of Ossicular Erosion in Human Acquired Cholesteatoma: An Immunohistochemical Study.Journal of clinical medicine · 2022Article
- Immunomodulation Effect of Biomaterials on Bone Formation.Journal of functional biomaterials · 2022Review
- Effects of WNT1 c.110 T>C and c.505G>T mutations on osteoblast differentiation via the WNT1/β-catenin signaling pathway.Journal of orthopaedic surgery and research · 2021Article
- Chronic inflammation of middle ear cholesteatoma promotes its recurrence via a paracrine mechanism.Cell communication and signaling : CCS · 2021Article
- Article
- Bone destruction in chronic otitis media is not mediated by the RANKL pathway or estrogen receptor-alpha.Science progressArticle
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cholesteatoma starts as a retraction of the tympanic membrane and expands into the middle ear, eroding the surrounding bone and causing hearing loss and other serious complications such as brain abscess and meningitis. Currently, the only effective treatment is complete surgical removal, but the recurrence rate is relatively high. In rheumatoid arthritis (RA), osteoclasts are known to be responsible for bone erosion and undergo differentiation and activation by receptor activator of NF-κB ligand (RANKL), which is secreted by synovial fibroblasts, T cells, and B cells. On the other hand, the mechanism of bone erosion in cholesteatoma is still controversial. In this study, we found that a significantly larger number of osteoclasts were observed on the eroded bone adjacent to cholesteatomas than in unaffected areas, and that fibroblasts in the cholesteatoma perimatrix expressed RANKL. We also investigated upstream transcription factors of RANKL using RNA sequencing results obtained via Ingenuity Pathways Analysis, a tool that identifies relevant targets in molecular biology systems. The concentrations of four candidate factors, namely interleukin-1β, interleukin-6, tumor necrosis factor α, and prostaglandin E2, were increased in cholesteatomas compared with normal skin. Furthermore, interleukin-1β was expressed in infiltrating inflammatory cells in the cholesteatoma perimatrix. This is the first report demonstrating that a larger-than-normal number of osteoclasts are present in cholesteatoma, and that the disease involves upregulation of factors related to osteoclast activation. Our study elucidates the molecular basis underlying bone erosion in cholesteatoma.
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Registered trials
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