Cranial base synchondrosis and condylar cartilage of temporo-mandibular joint in Cartilage Calcification Insufficient rat

• Project/Area Number: 15K11030
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Asahi University
• Principal Investigator: Nagayama Motohiko 朝日大学, 歯学部, 教授 (50298436)
• Co-Investigator(Kenkyū-buntansha): 田沼 順一 朝日大学, 歯学部, 教授 (20305139)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 軟骨内骨化 / インディアンヘッジホッグ / 軟骨細胞 / 形態変化 / ヘッジホッグシグナル / 細胞増殖転写因子 / Gli1 / PTHrP / 下顎頭軟骨 / 頭蓋底軟骨 / Ihh

Outline of Final Research Achievements

The cartilage calcification insufficient (CCI) rat derived from Sprague-Dawley (SD) rat (permeability=25%), show spontaneous skeletal dwarfism associated with delay of endochondral ossification including craniofacial development, limbs pseudoarticulation and excurvature. In this study, CCI rats (2 weeks after birth) showed abnormal endchondral occification including longitudinally wider length of intra-sphenoidal and spheno-occipital synchondrosis, and exhibited morphological hypertrophic cartilage of mandibular condyle compared to the normal SD rats. Real time PCR for Gli1 gene showed prominent relative increasing of transcription in CCI rats. This dwarf is up-regulated BrdU incorporation, over expression of Ihh, Smo and Gli1 mRNA.
The data demonstrate that CCI rats affect their endochondral ossification due to excessive Ihh signaling, which results in hyper proliferating but feed-back arrest of chondrocyte differentiation to remain the layer of chondrocytes in post-natal development.

Research Products

• [Journal Article] Establishment of a novel dwarf rat strain: cartilage calcification insufficient (CCI) rats (2015)
  • Author(s): Tanaka M1, Watanabe M, Yokomi I, Matsumoto N, Sudo K, Satoh H, Igarashi T, Seki A, Amano H, Ohura K, Kakei R, Shibata S, Nagayama M, Tanuma JI.
  • Journal Title: Experimental Animals Volume: 64 Issue: 2 Pages: 121-128
  • DOI: 10.1538/expanim.14-0072
  • NAID: 130005069857
  • ISSN: 0007-5124, 1341-1357, 1881-7122
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 軟骨石灰化不全（CCI）ラットの発症メカニズム 頭蓋底軟骨結合と下顎頭軟骨 (2017)
  • Author(s): 永山元彦, 田沼順一, 天野 均, 渡辺 実, 田中政巳
  • Organizer: 第59回歯科基礎医学会学術大会
• [Presentation] Mineral Trioxide Aggregate (MTA) with platelet-rich plasma can up-regulate the expression of DMP1 and Nestin following direct pulp capping in rat molar teeth (2016)
  • Author(s): Motohiko Nagayama, Maiko Yamada, Satoshi Kawano, Yoshiaki Takitani, Takakazu Yoshida and Yoshihiro Shibukawa
  • Organizer: IADR, Pulp Biology and Regeneration Group (PBRG) symposium 2016
  • Place of Presentation: Nagoya
  • Year and Date: 2016-06-26
  • Int'l Joint Research
• [Presentation] Fundamental studies of cytology by using a model animal. (2016)
  • Author(s): Hiroyasu Kaneko, Juna Nakao, Michiko Ehara, Motohiko Nagayama, Shinichiro Sumitomo, Jun-ichi Tanuma
  • Organizer: 19th International Congress of Cytology
  • Place of Presentation: Yokohama
  • Year and Date: 2016-05-28
  • Int'l Joint Research
• [Presentation] Study of Cartilage Calcification Insufficient (CCI) Rat (2016)
  • Author(s): Kohei Kuzushima, Aya Takeuchi, Motohiko Nagayama, Masami Tanaka, Minoru Watanabe, Hitoshi Amano, Jun-ichi Tanuma, Noriyuki Kitai
  • Organizer: 45th Annual Meeting of the AADR/40th Annual Meeting of the CADR
  • Place of Presentation: Los Angeles, CA, USA
  • Year and Date: 2016-03-16
  • Int'l Joint Research
• [Remarks] 研究テーマ
  • URL: http://scw.asahi-u.ac.jp/~patho/staff/index.html#staff02