Crosstalk between keratinocytes and fibroblasts : a mechanism underlying cholesteatoma induced bone destruction.

• Project/Area Number: 15K20204
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Osaka University
• Principal Investigator: IWAMOTO YORIKO 大阪大学, 医学系研究科, 特任研究員 (70636480)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 細胞間クロストーク / 角化扁平上皮細胞 / 線維芽細胞 / プロスタグランジンE2 / 破骨細胞 / RANKL / 炎症性サイトカイン / 角化重層扁平上皮

Outline of Final Research Achievements

I succeeded in generating in vivo and in vitro models for cholesteatoma tissue using keratinocytes and fibroblasts derived from mouse ear pinnae. With these models, I demonstrated that keratinocytes stimulate osteoclast differentiation through the induction of RANKL in fibroblasts. PGE2 significantly upregulated RANKL expression in fibroblasts , suggesting PGE2 is a candidate for a RANKL inducer.
Also in human cholesteatoma tissue, osteoclasts accumulated on the bone surface, and fibroblasts highly expressed RANKL.RNA sequence analysis of fibroblasts in perimatrix layer revealed highly expression of genes which involve in differentiation of osteoclasts.

Research Products

• [Int'l Joint Research] Institute of Molecular Biotechnology(Austria)
• [Journal Article] Intercellular communication between keratinocytes and fibroblasts induces local osteoclast differentiation: a mechanism underlying cholesteatoma-induced bone destruction (2016)
  • Author(s): Yoriko Iwamoto, Keizo Nishikawa, Ryusuke Imai, Masayuki Furuya, Maki Uenaka, Yumi Ohta, Tetsuo Morihana, Saori Itoi-Ochi, Josef M. Penninger, Ichiro Katayama, Hidenori Inohara, Masaru Ishii
  • Journal Title: Journal: Molecular and Cellular Biology Volume: 未定
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Interaction between keratinocytes and fibroblasts induces osteoclastogenesis: a mechanism underlying cholesteatoma-induced bone destruction (2016)
  • Author(s): Yoriko Iwamoto, Ryusuke Imai, Yumi Ohta, Tetsuo Morihana, Hidenori Inohara
  • Organizer: 10th international conference on cholesteatoma and ear surgery
  • Place of Presentation: Edinburgh, UK
  • Year and Date: 2016-06-05
• [Presentation] A novel experimental model for cholesteatoma-induced bone destruction. (2015)
  • Author(s): Yoriko Iwamoto, Keizo Nishikawa, Tetsuo Morihana, Takao Imai, Yumi Ohta, Yukiko Hanada, Ryusuke Imai, Masaru Ishii, HIdenori Inohara
  • Organizer: Politzer society meeting
  • Place of Presentation: 新潟
  • Year and Date: 2015-06-30
  • Int'l Joint Research