Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

Hansen, Torsten; Unger, Ronald E.; Gäumann, Andreas; Hundorf, Inga; Maurer, Jan; Kirkpatrick, Charles James; Kriegsmann, Jörg

doi:10.1038/modpathol.3880465

Cited by 33 publications

(31 citation statements)

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“…Furthermore, Olszewska et al [78] found higher serum concentration of HEX, β-glucuronidase, and β-galactosidase with resultant increase in glycoconjugate catabolism in the serum of cholesteatoma patients in comparison to healthy subjects. Finally, Hansen et al [79] found that cysteine proteinase cathepsin K was strongly expressed in cholesteatoma tissues particularly in osteoclasts at the site of bone destruction.…”

Section: Mechanisms Of Bone Resorption In Cholesteatomamentioning

confidence: 99%

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Hamed

Nakata

Sayed

et al. 2016

Clin Exp Otorhinolaryngol

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Cholesteatoma is a cystic non tumorous lesion of the temporal bone that has the ability to destroy nearby structures by its power to cause bone resorption and as a result, fatal complications prevail. We aimed to conduct a comprehensive review for pathogenesis of acquired cholesteatoma, bone resorption mechanisms, and offer a future vision of this serious disease. We have reviewed different theories for pathogenesis of acquired cholesteatoma including the most relevant and updated ones with special emphasis on the mechanisms of bone resorption through Medline/PubMed research using the keywords ‘aetiopathogenesis, bone resorption, acquired cholesteatoma, temporal bone, and cytokines.’ In order to strengthen our study, we searched the reference lists of identified reviews. Cholesteatoma is a subject of debate among otolaryngologists since it was prescribed firstly. Over many decades, several theories were postulated for aetiopathogenesis of cholesteatoma with a tendency to follow more than one theory to explain the proper nature of that disease. Until now, the mechanism of bone resorption has yet to be more clarified. In the last century, a leap has occurred in the field of biomolecular cholesteatoma research which improved our knowledge about its pathophysiology and bone destructive mechanism. However, surgery is still the only available treatment. We conclude that discovery of new therapeutic choices for cholesteatoma other than surgery by the use of anti-growth, anti-proliferative, apoptotic agents as well as medications that antagonize osteoclastogenesis should be the main concern in the future clinical and experimental research work. Also, searching for predictors of the aggressiveness of cholesteatoma can affect the timing of intervention and prevent occurrence of complications.

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Section: Mechanisms Of Bone Resorption In Cholesteatomamentioning

confidence: 99%

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Hamed

Nakata

Sayed

et al. 2016

Clin Exp Otorhinolaryngol

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“…In order to further explore the role of osteoclasts in bone erosion during osteonecrosis, we analyzed tissue specimens of patients with BON and IORN by immunohistochemistry with antibodies against cathepsin K. This cysteine proteinase is known to play a central role in osteoclast-mediated proteolytic degradation of collagen type I, which is the major organic constituent of the bone matrix [18]. Moreover, numerous studies indicate a predominant expression of cathepsin K in osteoclasts [11,12,18,36], and the enzyme has been suggested to be a good marker for activated osteoclasts [34]. We therefore analyzed cathepsin K expression in BON and IORN semiquantitatively and, in addition, compared the labeling results with control specimens.…”

Section: Introductionmentioning

confidence: 99%

Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in patients with infected osteoradionecrosis and bisphosphonate-associated osteonecrosis—a paradoxical observation?

2006

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Erosion of the bone is a common problem in patients suffering from infected osteoradionecrosis (IORN) or bisphosphonate-associated osteonecrosis (BON). Besides inflammatory mechanisms and infectious agents, osteoclasts were recently suggested to be specifically involved in the osteolytic mechanisms. We therefore investigated the immunohistochemical labeling of the cysteine proteinase cathepsin K, which plays a central role in osteoclast-mediated bone resorption, in tissue specimens of patients with BON (n=9; four male, five female; mean age=69.2 years) and IORN (n=10; nine male, one female; mean age=60.5 years), and compared the results with control specimens (n=8; six male, two female; mean age=60 years). In all cases, osteoclasts were the predominant cell type expressing cathepsin K. For semiquantitative analysis, we therefore defined osteoclasts as multinuclear giant cells attached to the bone and expressing cathepsin K. Significantly higher numbers of osteoclasts were found for both types of osteonecrosis when compared with the control group (BON+IORN vs controls: P=0.0000036). Within the pathological lesions, IORN cases exhibited significantly less osteoclasts than BON (P=0.00097). Our study verified increased numbers of osteoclasts in patients suffering from BON and IORN. Although it is known that bisphosphonates (and to a lesser extent, irradiation, too) decrease osteoclast function, these findings suggest a critical involvement of osteoclasts in the mechanisms of bone destruction in the respective lesions.

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“…Ferlito et al 8 suggested that the destructive property of cholesteatomas, bone erosion, is caused by the collagenases produced by the components of squamous and fibrous epithelial tissues. The hypothesis of bone absorption by biochemical action exclusively done by collagenolitic enzimes was later incorporated by other agents, such as tumor necrosis factor (TNF), interleukins (IL-1a) and prostaglandins (PGE2) [9][10][11] .…”

Section: Introductionmentioning

confidence: 99%

Correlação da cadeia ossicular no transoperatório com achados histológicos de colesteatomas

Dornelles

Rosito²,

Meurer³

et al. 2007

Rev. Bras. Otorrinolaringol.

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Chroni c otitis media is hystopathologycaly defined as the presence of irreversible inflammatory tissue changes in the middle ear. Ossicular lesions represent the most prevalent change. Aim: to correlate the degree of ossicular chain changes seen during surgery with the inflammatory histological degree and the thickness of the cholesteatoma perimatrix. Study design: Cross-sectional study. Methods: Seventyone descriptions of surgeries done in patients submitted to tympanomastoydectomy were reviewed. Cholesteatoma were collected and fixed in 10% formaldehyde. Two slides were made for each cholesteatoma, one stained with HE and another with picrossirius. Images were obtained from light microscopy and digitally processed and "blindly" analyzed using Image Pro-Plus Software. For statistical analysis we used Spearman's coefficient. Differences were considered statistically significant if P≤0.05. Results: the ossicular chain was involved in 65 cases. The incus was the most frequently affected bone, followed by the stapes and the malleus. When the Spearman's coefficient was employed considering ossicular chain change degree with patient's age by the time of surgery, perimatrix thickness and histological degree of inflammation, correlations were not established. Conclusion: Our findings indicate that ossicular chain changes are practically universal when a cholesteatoma is present. We didn't find correlations related with bone erosion and cholesteatoma's histological findings.

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Expression of Matrix-Degrading Cysteine Proteinase Cathepsin K in Cholesteatoma

Cited by 33 publications

References 31 publications

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Pathogenesis and Bone Resorption in Acquired Cholesteatoma: Current Knowledge and Future Prospectives

Increased numbers of osteoclasts expressing cysteine proteinase cathepsin K in patients with infected osteoradionecrosis and bisphosphonate-associated osteonecrosis—a paradoxical observation?

Correlação da cadeia ossicular no transoperatório com achados histológicos de colesteatomas

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