The roles of Cdc42 in intramembranous ossification via regulation of Ihh signaling

• Project/Area Number: 18K17076
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 57030:Conservative dentistry-related
• Research Institution: Showa University
• Principal Investigator: Aizawa Ryo 昭和大学, 歯学部, 助教 (80710673)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: Cdc42 / 頭蓋骨

Outline of Final Research Achievements

In the present study, we investigated the role of Cdc42 in cranial bone development. Our results showed that loss of Cdc42 caused a defect of intramembranous ossification in cranial bone tissues which is related to decreased expressions of cranial suture morphogenesis genes, including Indian hedgehog (Ihh) and bone morphogenetic proteins (BMPs). Inhibition of Cdc42 decreased expressions of Dlx5 and Igf1, which are related to osteoblast differentiation, in primary cultured mouse osteoblasts. These findings demonstrate that Cdc42 plays a crucial role in cranial osteogenesis, and is controlled by Ihh- and BMP-mediated signaling during cranium development.

Academic Significance and Societal Importance of the Research Achievements

個体レベルにおけるCdc42と膜性骨化に着目した研究はこれまでほとんどなく、特に頭蓋骨の縫合部でのCdc42の役割は明らかでなかった。本研究結果から、膜性骨化により形成される頭蓋骨において、Cdc42が重要な役割を果たしていることが示唆された。今後、Cdc42に着目した効率的な生体材料の作製への応用や骨破壊を伴う疾患の予防および治療に有用な手法を見出せる可能性がある。

Research Products

• [Journal Article] Visualization of junctional epithelial cell replacement by oral gingival epithelial cells over a life time and after gingivectomy. (2019)
  • Author(s): Kato M, Tanaka J, Aizawa R, Yajima-Himuro S, Seki T, Tanaka K, Yamada A, Ogawa M, Kamijo R, Tsuji T, Mishima K, Yamamoto M
  • Journal Title: Sci Rep Volume: 9 Issue: 1 Pages: 7640-7640
  • DOI: 10.1038/s41598-019-44065-x
  • Peer Reviewed / Open Access
• [Journal Article] Cdc42 regulates cranial suture morphogenesis and ossification (2019)
  • Author(s): Aizawa Ryo、Yamada Atsushi、Seki Tatsuaki、Tanaka Junichi、Nagahama Ryo、Ikehata Mikiko、Kato Tadashi、Sakashita Akiko、Ogata Hiroaki、Chikazu Daichi、Maki Koutaro、Mishima Kenji、Yamamoto Matsuo、Kamijo Ryutaro
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 512 Issue: 2 Pages: 145-149
  • DOI: 10.1016/j.bbrc.2019.02.106
  • Peer Reviewed / Open Access
• [Journal Article] Cdc42 regulates cranial suture morphogenesis and ossification (2019)
  • Author(s): Aizawa R, Yamada A, Seki T, Tanaka J, Nagahama R, Ikehata M, Kato T, Sakashita A, Ogata H, Chikazu D, Maki K, Mishima K, Yamamoto M, Kamijo R
  • Journal Title: Biochem Biophys Res Commun Volume: 印刷中
  • Peer Reviewed
• [Presentation] ハイドロキシアパタイト上での培養が不死化接合上皮細胞および口腔上皮細胞の遺伝子発現に及ぼす影響 (2019)
  • Author(s): 田中慧介，相澤 怜，田中準一，澤田直子，関 辰明，田中麻友，相内敏弘，板部洋之，美島健二，山本松男
  • Organizer: 第62回秋季日本歯周病学会学術大会
• [Presentation] 口腔歯肉上皮由来細胞による接合上皮細胞置換の可視化 (2019)
  • Author(s): 加藤麻友，田中準一，相澤 怜，氷室沙羅，関 辰明，田中慧介，山田 篤，上條竜太郎，美島健二，山本松男
  • Organizer: 第62回秋季日本歯周病学会学術大会
• [Presentation] Replacement of junctional epithelium by oral epithelium (2018)
  • Author(s): Kato M, Aizawa R, Tanaka J, Yajima-Himuro S, Seki T, Tanaka K, Mishima K, Yamamoto M
  • Organizer: 104th Annual Meeting of the American Academy of Periodontology in collaboration with the Japanese Society of Periodontology and the Japanese Academy of Clinical Periodontology
  • Int'l Joint Research
• [Presentation] 人工再構成歯胚技術を用いたマウス歯肉接合上皮細胞株の樹立 (2018)
  • Author(s): 関 辰明，相澤 怜，田中準一，氷室沙羅，加藤麻友，田中慧介，美島健二，山本松男
  • Organizer: 第61回秋季日本歯周病学会学術大会
• [Presentation] 歯胚移植技術を用いたマウス歯肉接合上皮構成細胞の経時的変化の解明 (2018)
  • Author(s): 加藤麻友，相澤 怜，関 辰明，田中慧介，美島健二，山本松男
  • Organizer: 第60回歯科基礎医学会学術大会
• [Presentation] 歯肉接合上皮構成細胞の経時的変化の解明 (2018)
  • Author(s): 加藤麻友，相澤 怜，田中準一，氷室沙羅，関 辰明，田中慧介，美島健二，山本松男
  • Organizer: 第347回昭和大学学士会例会
• [Remarks] 昭和大学歯学部口腔生化学講座
  • URL: http://www10.showa-u.ac.jp/~oralbio/index.html
• [Remarks] 昭和大学歯学部歯周病学講座
  • URL: http://www10.showa-u.ac.jp/~perio/index.html
• [Remarks] 昭和大学研究者情報・業績集
  • URL: https://researchers-achievements.showa-u.ac.jp/
• [Remarks] 昭和大学学術業績リポジトリ
  • URL: https://meta.lilitory.showa-u.ac.jp/