Cholesteatoma: Experimental Induction in the Mongolian Gerbil, Meriones Unguiculaus

McGinn, Michael D.; Chole, Richard A.; Henry, Kenneth R.

doi:10.3109/00016488209130853

Cited by 58 publications

(58 citation statements)

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“…Cholesteatomas were not only found to develop spontaneously with aging, but experimental cholesteatomas can also be induced by external auditory canal ligation (ECL) (11,12). Induced cholesteatomas progressively enlarge to an advanced stage of cholesteatoma over time.…”

Section: Introductionmentioning

confidence: 99%

Expression Patterns of Cytokeratins in Cholesteatomas: Evidence of Increased Migration and Proliferation

2002

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Aural cholesteatoma is characterized by invading squamous epithelia with altered growth properties. Cytokeratin (CK) expression is affected in epidermal proliferative diseases and represents the alterations of keratinocyte proliferation, differentiation, and migration. In the present study, the intensity of CK immuno-expression was determined, using densitometry at various sites in experimental cholesteatoma in order to characterize changes of keratinocytes. With cholesteatoma formation, CK4, a marker for non-keratinizing epithelia, increased in the suprabasal layers of the annular external auditory canal (EAC) and at the pars tensa indicating an altered differentiation and migration of keratinocytes. CK5/6, a marker of keratinizing squamous epithelium, increased only at the pars tensa of the tympanic membrane, indicating basal keratinocyte hyperplasia. CK1/10 increased in the suprabasal layer at the annular EAC, and at the peripheral pars tensa, indicating increased terminal differentiation of keratinocytes. CK13/16, markers of differentiation and hyperproliferation, increased in suprabasal layer of the EAC, and at the peripheral pars tensa. However, it decreased in the basal layer of the EAC, indicating hyperproliferation and migration of keratinocytes. The findings of this study support the basal cell hyperplasia hypotheses for the pathogenesis of aural cholesteatoma, with regard to hyperproliferation, migration, and an altered differentiation of keratinocytes.

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Section: Introductionmentioning

confidence: 99%

Expression Patterns of Cytokeratins in Cholesteatomas: Evidence of Increased Migration and Proliferation

2002

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“…An animal model of cholesteatoma was induced in gerbil with the EAC ligation method (Figure 1, A-C). 12 The right ear canals of each gerbil were ligated with 4-0 silk suture through a curvilinear incision behind the pinna (Hybrid model group, Figure 1A). As controls, five male and five female gerbils (12 weeks old) with normal eardrums and without myringoplasty were used, and right EAC was ligated to make experimental cholesteatoma (control group, Figure 1B and C).…”

Section: Animals and Tissue Preparationmentioning

confidence: 99%

“…11 In addition to developing spontaneously with aging, cholesteatomas can be experimentally induced via EAC ligation in the gerbil. 12 To investigate the origin of the epithelial cells of cholesteatoma, whether from the epithelial cells of EAC or tympanic membrane, we made a new model of experimentally induced cholesteatoma in gerbils and use a new analysis system named in situ PCR. 14 …”

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Pathogenesis of Middle Ear Cholesteatoma

Yamamoto‐Fukuda

Hishikawa

Shibata

et al. 2010

The American Journal of Pathology

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Middle ear cholesteatoma is characterized by enhanced proliferation of epithelial cells with aberrant morphological characteristics. To investigate the origin of the cholesteatoma cells, we analyzed spontaneously occurring cholesteatomas associated with a new transplantation model in Mongolian gerbils (gerbils). Cholesteatomas were induced in gerbils with a transplanted tympanic membrane by using the external auditory canal (EAC) ligation method. After the pars flaccida of the tympanic membranes were completely removed from male gerbils, corresponding portions of tympanic membranes of female gerbils were transplanted to the area of defect, and then we ligated the EAC (hybrid-model group). As a control group, the EAC of normal male and female gerbils was ligated without myringoplasty. In all ears of each group, the induced cholesteatomas were seen. In situ PCR was then performed to detect the mouse X chromosomelinked phosphoglycerate kinase-1 (pgk-1) gene on the paraffin sections. One pgk-1 spot in the epithelial nuclei was detected in male cholesteatoma, and two pgk-1 spots were detected in female cholesteatoma, respectively. On the other hand, in the hybrid-model group, we detected not only one but also two pgk-1 spots in the epithelial nuclei of cholesteatoma. These results strengthened the evidence that the origin of epithelial cells in cholesteatoma is the tympanic membrane in this model, but not the residential middle ear epithelial cells or the skin of the EAC. (Am J

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“…The Mongolian gerbil develops spontaneous cholesteatoma (47)(48)(49), which is known to cause bone resorption and is used as a cholesteatoma model. Additionally, chinchillas and guinea pigs have been used as cholesteatoma models (50,51).…”

Section: Discussionmentioning

confidence: 99%

Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction

Iwamoto

Nishikawa

Imai

et al. 2016

Molecular and Cellular Biology

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Bone homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. Shifting the balance toward bone resorption causes osteolytic bone diseases such as rheumatoid arthritis and periodontitis. Osteoclast differentiation is regulated by receptor activator of nuclear factor B ligand (RANKL), which, under some pathological conditions, is produced by T and B lymphocytes and synoviocytes. However, the mechanism underlying bone destruction in other diseases is little understood. Bone destruction caused by cholesteatoma, an epidermal cyst in the middle ear resulting from hyperproliferation of keratinizing squamous epithelium, can lead to lethal complications. In this study, we succeeded in generating a model for cholesteatoma, epidermal cyst-like tissue, which has the potential for inducing osteoclastogenesis in mice. Furthermore, an in vitro coculture system composed of keratinocytes, fibroblasts, and osteoclast precursors was used to demonstrate that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. Thus, this study demonstrates that intercellular communication between keratinocytes and fibroblasts is involved in the differentiation and function of osteoclasts, which may provide the molecular basis of a new therapeutic strategy for cholesteatoma-induced bone destruction. Bone is a highly dynamic organ in which homeostasis is maintained by a balance in activity between bone-resorbing osteoclasts and bone-forming osteoblasts. An imbalance between osteoclastic and osteoblastic activity causes various skeletal disorders. Osteoclasts are multinucleate cells that differentiate from mononuclear macrophage/monocyte-lineage hematopoietic precursor cells, which are attracted to the bloodstream by factors, including sphingsine-1 phosphate (1, 2). Osteoclast differentiation and function are regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor B ligand (RANKL) (3-5). Under physiological conditions, osteoblasts or osteocytes are the source of RANKL (6-8). RANKL-mediated osteoclastogenesis also plays an important role in bone destruction in inflammatory bone diseases such as rheumatoid arthritis (RA) or periodontal diseases. In such pathological states, synoviocytes or immune cells, such as B or T lymphocytes, infiltrating into the area are proposed to be the major sources of RANKL (9-11). In RA, infiltration of T helper 17 (Th17) cells is observed in the synovium. Th17 cells indirectly induce RANKL expression in synoviocytes by producing interleukin-17 (IL-17) (12), and Th17 cells themselves express RANKL on their plasma membrane (13). Thus, in many bone destructive diseases, the mechanisms of bone destruction are becoming clarified in detail. However, there are still certain bone destructive diseases whose underlying mechanisms remain to be elucidated. Cholesteatoma, a benign entity arising in temporal bone, is one such disease where our understanding is limited.Cholesteatoma is an epid...

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Cholesteatoma: Experimental Induction in the Mongolian Gerbil, Meriones Unguiculaus

Cited by 58 publications

References 10 publications

Expression Patterns of Cytokeratins in Cholesteatomas: Evidence of Increased Migration and Proliferation

Expression Patterns of Cytokeratins in Cholesteatomas: Evidence of Increased Migration and Proliferation

Pathogenesis of Middle Ear Cholesteatoma

Intercellular Communication between Keratinocytes and Fibroblasts Induces Local Osteoclast Differentiation: a Mechanism Underlying Cholesteatoma-Induced Bone Destruction

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