Mechanismofboneresorption inmiddleearcholesteatoma inthe light of H^+ concentration and H^+-sensing Proteins

2012 Fiscal Year Final Research Report

• Project/Area Number: 22591893
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: University of Occupational and Environmental Health, Japan
• Principal Investigator: SUZUKI Hideaki 産業医科大学, 医学部, 教授 (20187751)
• Co-Investigator(Kenkyū-buntansha): WAKASUGI Tetsuro 産業医科大学, 医学部, 助教 (20461569) ; HASHIDA Koichi 産業医科大学, 医学部, 講師 (90389461) ; SHIBATA Minori 産業医科大学, 医学部, 講師 (90512187)
• Project Period (FY): 2010 – 2012
• Keywords: 中耳真珠腫 / 水素イオン / 骨吸収 / バリア機能 / pH / フィラグリン / 電子顕微鏡 / 共焦点レーザー操作顕微鏡

Research Abstract

Objective:The etiopathology of bone resorption in cholesteatoma is unclear. We studied pH inmiddle ear cholesteatoma tissue and the permeability of the cholesteatoma epithelium in an attempt to elucidate the mechanism of bone resorption in this disease.
Methods:Cholesteatoma tissue was collected from patients with primary acquired middle ear cholesteatoma. The pH of the keratin debris of cholesteatoma was measured using a pH meter. The cholesteatoma epithelium was examined under a confocal laser scanning microscope, and under a transmission electron microscope. Expression of filaggrin in the cholesteatoma tissue was explored by fluorescence immunohistochemistry and by quantitative reverse transcription-polymerase chain reaction.
Results: The pH of the keratin debris of cholesteatoma was acidic. The pH of the basal layer of the cholesteatoma epithelium was significantly lower than that of the antrum mucosa. Transmission electron microscope showed distinct penetration of lanthanum in the intercellular space of the basal, spinous and granular layers of the cholesteatoma epithelium, but only a small amount of lanthanum in the granular layer in the normal skin. The expression of filaggrin nlRNA was significantly lower in the cholesteatoma tissue than in the normal skin.
Conclusions: These results indicate that acid leakage through the cholesteatonla epitheliunl probably participates in the resorption of the underlying bone structure. The increased permeability of the cholesteatoma epitheliunl may be explained by a decrease in filaggrin expression.

Research Products

• [Journal Article] Possible participation of acidic pH in bone resorption in middle ear cholesteatoma
  • Author(s): Nguyen KH, Suzuki H, Ohbuchi T, wakasugi T, Koizumi H, Hashida K, Baba R, Morimoto H, Doi Y
  • Journal Title: Laryngoscope Volume: (in press)
  • DOI: DOI:10.1002/lary.23245
  • Peer Reviewed
• [Presentation] 中耳真珠腫組織のpHと骨吸収機序 (2013)
  • Author(s): 鈴木秀明,グェン カク ホン,若杉哲郎,大淵豊明,小泉弘樹,橋田光一
  • Organizer: 第114回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: 札幌
  • Year and Date: 2013-05-16
• [Presentation] 中耳真珠腫組織pHの骨吸収機序への関与 (2012)
  • Author(s): 鈴木秀明,グェン カク ホン,大淵豊明,小泉弘樹,橋田光一
  • Organizer: 第22回日本耳科学会総会学術講演会
  • Place of Presentation: 名古屋
  • Year and Date: 2012-10-04
• [Remarks] [1] Iino Y, et al.: Organic acids and anaerobic microorganisms in the contents of the cholesteatoma sac. Ann Otol Rhinol Laryngol 92: 91-96, 1983
• [Remarks] [2] Pereverzev A, et al.: Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway. Bone 42: 150-161, 2008.
• [Remarks] [3] Yanlamura H, et al.: Protons activate theδ-subunit of the epithelial Na^+channel in humans. J Bio Chem 279: 12529-12534, 2004.