Osteoclast Stimulating and Differentiating Factors in Human Cholesteatoma

Hamzei, Michael; Ventriglia, Giovanni; Hagnia, Mitra; Antonopolous, Alexandra; Bernal‐Sprekelsen, Manuel; Dazert, Stefan; Hildmann, H.; Sudhoff, Holger

doi:10.1097/00005537-200303000-00009

Cited by 55 publications

(51 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, the detailed etiology of the bone destruction in COM remains unclear. Resorption of audiological ossicles occurs in a localized area adjacent to the cholesteatoma perimatrix or granulation tissue [4][5][6] . The perimatrix of cholesteatoma contains lymphocytes, monocytes, fibroblasts and endothelial cells that are the source of high concentrations of proinflammatory (TNF-␣ , IL-1 and IL-6) and immunoregulatory (IL-2, IL-4, IL-5, IL-10, TGF-␤ and GM-CSF) cytokines and other mediators (RANKL) [2,5,7,8] .…”

Section: Introductionmentioning

confidence: 99%

“…Activated osteoclasts play the main role in the osteolysis process in COM [2,8,9] . Proinflammatory cytokines produced by cholesteatoma may activate osteoclasts involved in the bone osteolysis, stimulate keratinocytes and endothelial cells, and may activate the selectins and integrins enabling the rolling and adhesion processes [2,6,[9][10][11] . In cholesteatoma increased concentrations of TNF-␣ , IL-1 ␣ and IL-6 were observed [2,7,9,10] .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Expression of Tumor Necrosis Factor-α, Interleukin-1α, Interleukin-6 and Interleukin-10 in Chronic Otitis Media with Bone Osteolysis

Kuczkowski¹,

Sakowicz-Burkiewicz

Iżycka‐Świeszewska

et al. 2011

ORL

View full text Add to dashboard Cite

The purpose of this study was to evaluate the expression of proinflammatory and immunoregulatory cytokines in chronic otitis media. The expression levels of TNF-α, IL-1α, IL-6 and IL-10 were determined by Western blot analysis of tissue samples obtained during ear surgery. The expression levels of TNF-α, IL-1α and IL-6 in cholesteatoma tissues were substantially higher compared to those determined in the granulation tissue. The highest levels of TNF-α, IL-1 and IL-6 proteins were observed in patients with bone destruction. There were no significant differences in the expression of IL-10 levels in cholesteatoma and normal skin, but in the granulation tissue its level was substantially higher. The level of IL-10 in cholesteatoma tissues inversely correlated with the expression of proinflammatory cytokines, the degree of bone destruction and cholesteatoma invasion. Increased expressions of TNF-α, IL-1α and IL-6 in chronic otitis media and a strong positive correlation between these cytokine levels and the degree of bone destruction indicate the destructive behavior of cholesteatoma or granulation tissue.

show abstract

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Expression of Tumor Necrosis Factor-α, Interleukin-1α, Interleukin-6 and Interleukin-10 in Chronic Otitis Media with Bone Osteolysis

Kuczkowski¹,

Sakowicz-Burkiewicz

Iżycka‐Świeszewska

et al. 2011

ORL

View full text Add to dashboard Cite

show abstract

“…However, the localization of RANKL is also controversial. Some have reported it is expressed in the epithelial layer (43), others showed it was expressed in the subepithelial layer, including infiltrated inflammatory cells (44), and still others found both the epithelial layer and subepithelial layer (45,46) expressed RANKL in cholesteatoma. What makes these problems difficult to solve is partially that cholesteatoma is usually removed piece by piece, and the obtained clinical samples are very small.…”

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

View full text Add to dashboard Cite

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...

show abstract

“…Florid inflammation and angiogenesis are distinctive features of the condition in most cases. It is also believed that the inflammation associated within the perimatrix of cholesteatoma induces bone resorption [17] . It is suspected that an early treatment of the inflammatory process of the ear may probably prevent the development of hyperplastic destructive epidermis [7] .…”

Section: Definitionsmentioning

confidence: 99%

Cholesteatoma Definition and Classification: A Literature Review

Rutkowska

Özgirgin²,

Olszewska³

2017

Int Adv Otol

View full text Add to dashboard Cite

Review INTRODUCTIONThe management of cholesteatoma continues to be a challenge for otolaryngologists around the world. Even in countries with advanced healthcare facilities, undertaking routine physical examinations, with good access to specialists, and where efforts are taken for the prevention, early detection, and treatment of cholesteatoma, there is a considerable prevalence of cholesteatoma and its complications in children and adults.Diagnosis of cholesteatoma is performed by otolaryngologists using different methods, including obtaining the history that is characteristic for cholesteatoma suspicion, searching for or evidence of cholesteatoma during the physical examination using otoscopy and/or otomicroscopy, and interpretation of imaging (computed tomography and/or magnetic resonance) [1].Despite the fact that cholesteatoma is diagnosed throughout the world, there are differences in the definition, classification, and management of cholesteatoma. These differences make it difficult to compare the reports in the literature, and limit the ability to derive further conclusions from individual or regional outcomes. Therefore, it is essential to create a common scientific language, with the definitions of an issue as a principle. Furthermore, utilizing a comparable classification system will allow investigators to share their experience across the world, leading to better assessment and management of cholesteatoma.To achieve this, a recent initiative aimed to explore opinions among the members of European Academy of Otology & Neuro-otology (EAONO) regarding the definition and classification of cholesteatoma. Although consensus was achieved on the cholesteatoma definitions, it could not be achieved on its classification [2] . The process of development of the questionnaires, the responses obtained from the EAONO members through three cycles of questionnaires, and the final set of statements were reported in detail. Here we report the literature review that led to the development of the questionnaire on the definitions and classification to provide a basis for the outcome. In addition, we present various classifications of cholesteatoma in the literature and emphasize the strengths and weaknesses of each of these classifications to stimulate an effort to develop a consensus on the classification as well. METHODSEAONO steering group decided to undertake the task of developing guidelines in the field of otology and neurotology. Guidelines regarding the assessment and management of cholesteatoma were established as a priority. Among the committees established, the task of developing the guidelines for the definition and classification of cholesteatoma was assigned to Ewa Olszewska in June Cholesteatoma Definition and Classification: A Literature ReviewCholesteatoma is a serious otolaryngologic condition that to date remains an important problem and poses a challenge to otolaryngologists around the world. To improve the approach pertaining to the diagnosis and management of middle ear cholesteatoma, clear, clinical...

show abstract

Osteoclast Stimulating and Differentiating Factors in Human Cholesteatoma

Cited by 55 publications

References 21 publications

Expression of Tumor Necrosis Factor-α, Interleukin-1α, Interleukin-6 and Interleukin-10 in Chronic Otitis Media with Bone Osteolysis

Expression of Tumor Necrosis Factor-α, Interleukin-1α, Interleukin-6 and Interleukin-10 in Chronic Otitis Media with Bone Osteolysis

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

Cholesteatoma Definition and Classification: A Literature Review

Contact Info

Product

Resources

About