Mechanism of bone resorption in middle ear cholesteatoma in the light of epithelial barrier function

• Project/Area Number: 25462656
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• 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): HASHIDA Koichi 産業医科大学, 医学部, 講師 (90389461) ; WAKASUGI Tetsuro 産業医科大学, 医学部, 助教 (20461569) ; OHBUCHI Toyoaki 産業医科大学, 医学部, 助教 (00412651) ; KOIZUMI Hiroki 産業医科大学, 医学部, 助教 (70461572)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 中耳真珠腫 / 骨吸収 / pH / 上皮バリア / 透過性 / 破骨細胞 / バリア機能 / 非脱灰骨切片 / イソペプチド結合 / トランスグルタミナーゼ / コルネオデスモシン / 電気的インピーダンス / フィラグリン / クロージン / トリセルリン

Outline of Final Research Achievements

Middle ear cholesteatoma is an epidermal cyst with keratin debris accumulating inside that has acidic pH. Generally speaking, the surface of normal epidermis is maintained acidic, however, barrier function of the horny and granular layers protects subepidermal tissues from the acidic environment. On the other hand, barrier function of the cholesteatoma epithelium is impaired, resulting in an increased permeability. Impaired barrier function is explained by an decease in the expressions of filaggrin and corneodesmosin in the horny layer and claudin-1, claudin-3 and tricellulin in the granulara layer. These lines of evidence supports the acid lysis theory that the cholesteatoma epithelium has impaired barrier function and leaks the acidity of its contents, leading to the resorption of the underlying bone.

Research Products

• [Journal Article] Osteoclasts are not activated in middle ear cholesteatoma. (2016)
  • Author(s): Koizumi H, Suzuki H, Ikezaki S, Ohbuchi T, Hashida K, Sakai A
  • Journal Title: J Bone Miner Metab Volume: 34 Issue: 2 Pages: 193-200
  • DOI: 10.1007/s00774-015-0655-5
  • Peer Reviewed
• [Journal Article] Electrical impedance and expression of tight junction components of the nasal turbinate and polyp (2016)
  • Author(s): Suzuki H, Koizumi H, Ikezaki S, Tabata T, Ohkubo J-I, Kitamura T, Hohchi N
  • Journal Title: ORL Journal for Oto-Rhino-Laryngology, Head and Neck Surgery Volume: 78 Issue: 1 Pages: 16-25
  • DOI: 10.1159/000442024
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Increased permeability of the epithelium of middle ear cholesteatoma (2015)
  • Author(s): Koizumi H, Suzuki H, Ohbuchi T, Kitamura T, Hashida K, Nakamura M
  • Journal Title: Clinical Otolaryngology Volume: 40 Issue: 2 Pages: 106-114
  • DOI: 10.1111/coa.12332
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Possible participation of acidic pH in bone resorption in middle ear cholesteatoma. (2014)
  • Author(s): Nguyen KH, Suzuki H, Ohbuchi T, Wakasugi T, Koizumi H, Hashida K, Baba R, Morimoto H, Doi Y.
  • Journal Title: Laryngoscope. Volume: 124(1) Issue: 1 Pages: 245-50
  • DOI: 10.1002/lary.23883
  • Peer Reviewed
• [Presentation] 中耳真珠腫における骨吸収機序に破骨細胞は関与しない (2015)
  • Author(s): 小泉弘樹、池嵜祥司、橋田光一、寳地信介、鈴木秀明
  • Organizer: 第25回日本耳科学会
  • Place of Presentation: 長崎ブリックホール（長崎県・長崎市）
  • Year and Date: 2015-10-08
• [Presentation] 真珠腫上皮における透過性の検討 (2015)
  • Author(s): 小泉弘樹、橋田光一、池嵜祥司、鈴木秀明
  • Organizer: 第116回日本耳鼻咽喉科学会
  • Place of Presentation: 東京国際フォーラム（東京都・千代田区）
  • Year and Date: 2015-05-21
• [Presentation] 中耳真珠腫組織のpHと骨吸収機序 (2013)
  • Author(s): 鈴木秀明、Nguyen Khac-Hung、若杉哲郎、大淵豊明、小泉弘樹、橋田光一
  • Organizer: 日本耳鼻咽喉科学会
  • Place of Presentation: 札幌、ロイトン札幌