Expression levels of receptor activator of nuclear factor-κB ligand and osteoprotegerin are associated with middle ear cholesteatoma risk

Chen, Aiping; Wang, Bin; Zhong, Feng; Song, Guizhen; Song, Hong-Fu; Yu, Kun; Wang, Haibo; Jiang, Zhenhua

doi:10.3109/00016489.2015.1011789

Cited by 11 publications

(5 citation statements)

References 15 publications

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“…Multiple studies have shown that bone destruction in cholesteatoma is mediated by the RANKL pathway. 3,4,23 Conversely, some studies have revealed potential mechanisms of bone resorption in cholesteatoma that are independent of the RANKL pathway or osteoclast activation 24,25 ; the results of the present study were consistent with those findings. Notably, estrogen plays an osteoprotective role in osteoporosis by regulating the RANKL pathway.…”

Section: Discussionsupporting

confidence: 92%

Bone destruction in chronic otitis media is not mediated by the RANKL pathway or estrogen receptor-alpha

Heo,

Noh,

Hur

et al. 2023

Science Progress

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Background Chronic otitis media with or without cholesteatoma progresses with various degrees of bone resorption and remodeling. Estrogen mediates osteoprotective effects through the receptor activator of NF-κB ligand (RANKL) pathway, which is mainly mediated by estrogen receptor-alpha (ER-α). Objectives The present study investigated the expression patterns of receptor activator of NF-κB (RANK), osteoprotegerin (OPG), RANKL, and ER-α in pathological tissue from patients with chronic otitis media to determine the roles of those factors in osteolytic mechanisms underlying the pathogenesis of chronic otitis media. Methods Normal and pathological specimens from 18 patients with chronic otitis media were examined. Results There were no significant differences in RANK, OPG, RANKL, or ER-α mRNA expression between normal and pathological specimens of epithelial tissue. Conclusions Our findings suggested that RANK, OPG, RANKL, and ER-α are not associated with the bone destruction in chronic otitis media; other cytokines may directly activate the osteoclasts in chronic otitis media.

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Section: Discussionsupporting

confidence: 92%

Bone destruction in chronic otitis media is not mediated by the RANKL pathway or estrogen receptor-alpha

Heo,

Noh,

Hur

et al. 2023

Science Progress

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“…In accordance with this RANKL-positive cells and/or the ratio of RANKL/OPG were significantly higher in MEC compared to every other skin sample e.g. external meatal skin [ 186 , 187 ], post auricular skin [ 188 ] normal skin [ 189 ], auditory canal skin and even granulation tissues [ 190 ] and RANKL expression positively correlated with osteolysis in MEC patients [ 186 , 191 ]. In contrast to the upregulation of RANKL in the soft body tissue adjacent to the decomposing bone, there was no evidence found for an increase in RANKL or RANKL/OPG ration inside the bone tissue more distant to MEC [ 192 ].…”

Section: Applicable Targets In Precision Medicine For Mec Therapymentioning

confidence: 52%

Review of potential medical treatments for middle ear cholesteatoma

2022

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Middle ear cholesteatoma (MEC), is a destructive, and locally invasive lesion in the middle ear driven by inflammation with an annual incidence of 10 per 100,000. Surgical extraction/excision remains the only treatment strategy available and recurrence is high (up to 40%), therefore developing the first pharmaceutical treatments for MEC is desperately required. This review was targeted at connecting the dysregulated inflammatory network of MEC to pathogenesis and identification of pharmaceutical targets. We summarized the numerous basic research endeavors undertaken over the last 30+ years to identify the key targets in the dysregulated inflammatory pathways and judged the level of evidence for a given target if it was generated by in vitro, in vivo or clinical experiments. MEC pathogenesis was found to be connected to cytokines characteristic for Th1, Th17 and M1 cells. In addition, we found that the inflammation created damage associated molecular patterns (DAMPs), which further promoted inflammation. Similar positive feedback loops have already been described for other Th1/Th17 driven inflammatory diseases (arthritis, Crohn’s disease or multiple sclerosis). A wide-ranging search for molecular targeted therapies (MTT) led to the discovery of over a hundred clinically approved drugs already applied in precision medicine. Based on exclusion criteria designed to enable fast translation as well as efficacy, we condensed the numerous MTTs down to 13 top drugs. The review should serve as groundwork for the primary goal, which is to provide potential pharmaceutical therapies to MEC patients for the first time in history.

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“…A particularly high concentration of avb3 integrins has been demonstrated on the surface of osteoclasts. 16,17 After joining the surface of a bone, osteoclasts polarize their structure to create 3 morphologically and functionally different areas of the cell membrane: the basolateral membrane, which is rich in integrins and is not in contact with the bone, and a bright adhesion zone and ruffled border, very characteristic of osteoclasts. The adhesion zone is essential for closing the resorptive bay, that is, the space between the ruffled border and the bone, where very low pH values predominate.…”

Section: Discussionmentioning

confidence: 99%

Patterns of Bone Damage in Patients With Chronic Middle Ear Inflammation

2020

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Background: Despite different etiologies, chronic otitis media involves the damaging and restructuring of bone tissue. The inflammatory process destroys elements of the ossicular chain, and bone lesions may appear that allow the development of otogenous complications. Aims/Objectives: A correlation between the degree of damage to the ossicular chain as well as the bony walls of the middle ear and the type of chronic inflammatory lesions was sought. Destructive changes to bones were observed using scanning microscopy. Material and Methods: The removed damaged fragments of the ossicles were prepared for evaluation with a scanning microscope. Preparations were sputter-coated with a thin layer of gold and subsequently evaluated. Results: Of 220 surgeries carried out in the discussed period, destruction of the middle ear bone walls, opening the way for the development of intracranial complications, was found in 27 patients. Most of them had ongoing chronic otitis media with granulation. Conclusions: (1) Bone loss of the skull base was observed more frequently in patients with chronic otitis media with granulation than with cholesteatoma. (2) In chronic otitis media with cholesteatoma, damage to the ossicular chain was observed significantly more frequently than in the case of otitis media with granulation.

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Expression levels of receptor activator of nuclear factor-κB ligand and osteoprotegerin are associated with middle ear cholesteatoma risk

Cited by 11 publications

References 15 publications

Bone destruction in chronic otitis media is not mediated by the RANKL pathway or estrogen receptor-alpha

Bone destruction in chronic otitis media is not mediated by the RANKL pathway or estrogen receptor-alpha

Review of potential medical treatments for middle ear cholesteatoma

Patterns of Bone Damage in Patients With Chronic Middle Ear Inflammation

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