Is epithelial-mesenchymal transition of stellate reticulum cells in enamel organ associated with induction of vasculogenesis?

• Project/Area Number: 24659818
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Morphological basic dentistry
• Research Institution: Iwate Medical University
• Principal Investigator: HARADA Hidemitsu 岩手医科大学, 歯学部, 教授 (70271210)
• Co-Investigator(Kenkyū-buntansha): HARADA Hidemitsu 岩手医科大学, 歯学部, 教授 (70271210) ; IDA Hiroko 新潟大学, 医歯学系, 准教授 (60293213) ; OTSU Keishi 岩手医科大学, 歯学部, 助教 (60509066) ; ISEKI Sachiko 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (80251544)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 歯の発生 / 血管新生 / 上皮間葉転換 / エナメル器 / 星状網 / 血管構築

Research Abstract

In the late stage of tooth germ development, vasculogenesis is observed in the enamel organ. To discover the mechanisms of the vasculogenesis, we studied on the relationship between the vasculogenesis and epithelial-mesenchymal transition using Keratin14 cre-b-gal transgenic mouse, Mesp1 cre-b-gal transgenic mouse and Flk1-GFP transgenic mouse. Also, the cell dynamics of enamel organ was observed by real-time imaging of tooth germ organ culture. The study showed that the development of stellate reticulum cells is derived from inner enamel epithelial cells, and that the vasculogenesis and epithelial-mesenchymal transition is closely associated with hypoxia in the enamel organ from expression of Hif1. Furthermore, it is considered that the vasculogenesis is related with ameloblast differentiation to calcify the enamel matrix.

Research Products

• [Journal Article] Wntl 1 expression in rat dental pulp and promotional effects of Wnt signaling on odontoblast differentiation (2013)
  • Author(s): Koizumi Y, Kawashima N, Yamamoto M, Takimoto K, Zhou M, Suzuki N, Saito M, Harada H, Suda H
  • Journal Title: Congenit Anom(Kyoto) Volume: 53(3) Pages: 101-8
  • Peer Reviewed
• [Journal Article] Enamel defects reflect perinatal exposure to bisphenol A (2013)
  • Author(s): Jedeon K, De la Dure-Molla M, Brookes SJ, Loiodice S, Marciano C, Kirkham J, Canivenc-Lavier MC, Boudalia S, Berges R, Harada H, Berdal A, Babajko S
  • Journal Title: Am J Pathol Volume: 183(1) Issue: 1 Pages: 108-18
  • DOI: 10.1016/j.ajpath.2013.04.004
  • Peer Reviewed
• [Journal Article] Reciprocal expressions between α-dystroglycan and integrin β1, perlecan receptors, in the murine enamel organ development. (2013)
  • Author(s): Ida-Yonemochi H, Harada H, Ohshima H, Saku T
  • Journal Title: Gene Expr Patterns Volume: 13 Issue: 8 Pages: 293-302
  • DOI: 10.1016/j.gep.2013.05.004
  • Peer Reviewed
• [Journal Article] Circadian rhythms regulate amelogenesis (2013)
  • Author(s): Zheng L, Seon YJ, Mourao MA, Schnell S, Kim D, Harada H, Papagerakis S, Papagerakis P
  • Journal Title: Bone Volume: 55(1) Issue: 1 Pages: 158-65
  • DOI: 10.1016/j.bone.2013.02.011
  • Peer Reviewed
• [Journal Article] Expression of antimicrobial peptides and E-cadherin in periapical lesions (2013)
  • Author(s): Ishihata K, Kume K, Hijioka H, Kibe T, Tanaka S, Komatsuzawa H, Harada H, Nakamura N
  • Journal Title: Oral Science International Volume: Volume 10, Issue 2 Pages: 70-76
  • Peer Reviewed
• [Journal Article] Characterization of Dental Epithelial Stem Cells from the Mouse Incisor with 2D and 3D Platforms (2013)
  • Author(s): Chavez MG, Yu W, Biehs B, Harada H, Snead ML, Klein OD
  • Journal Title: Tissue Eng Part C Methods Volume: 19(1) Pages: 15-24
  • Peer Reviewed
• [Journal Article] Cell dynamics in cervical loop epithelium during transition from crown to root : implications for Hertwig's epithelial root sheath formation (2013)
  • Author(s): Sakano M, Otsu K, Fujiwara N, Fukumoto S, Yamada A, Harada H
  • Journal Title: J Periodontal Res Volume: 48 Pages: 262-267
  • Peer Reviewed
• [Journal Article] Cell dynamics in cervical loop epithelium during transition from crown to root: implications for Hertwig's epithelial root sheath formation. (2013)
  • Author(s): Sakano M, Otsu K, Fujiwara N, Fukumoto S, Yamada A, Harada H
  • Journal Title: Journal of periodontal Research Volume: 48 Issue: 2 Pages: 262-267
  • DOI: 10.1111/jre.12003
  • Peer Reviewed
• [Journal Article] Characterization of Dental Epithelial Stem Cells from the Mouse Incisor with 2D and 3D Platforms. (2013)
  • Author(s): Chavez MG, Yu W, Biehs B, Harada H, Snead ML, Klein OD
  • Journal Title: Tissue Eng Part C Methods. Volume: 19(1) Issue: 1 Pages: 15-24
  • DOI: 10.1089/ten.tec.2012.0232
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth (2012)
  • Author(s): Sakuraba H, Fujiwara N, Sasaki-Oikawa A, Sakano M, Tabata, Y, Otsu K, Ishizeki K, Harada H
  • Journal Title: J Periodontal Res Volume: 47(1) Pages: 81-88
  • Peer Reviewed
• [Journal Article] Differentiation of induced pluripotent stem cells into dental mesenchymal cells (2012)
  • Author(s): Otsu K, Kishigami R, Oikawa-Sasaki A, Fukumoto S, Yamada A, Fujiwara N, Ishizeki K, Harada H
  • Journal Title: Stem Cells Dev Volume: 21(7) Pages: 1156-64
  • Peer Reviewed
• [Journal Article] Histological analysis of epithelial stem cells during induced pluripotent stem cell-derived teratoma development (2012)
  • Author(s): Kishigami, R., Otsu, K., Oikawa-Sasaki, A., Fujiwara, N., Ishizeki, K., Tabata, Y., Harada, H
  • Journal Title: J. Oral Biosci Volume: 54 Pages: 58-65
  • Peer Reviewed
• [Journal Article] Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars (2012)
  • Author(s): Ida-Yonemochi, H., Nakatomi, M., Harada, H., Takata, H., Baba, 0., Ohshima, H
  • Journal Title: Dev. Biol Volume: 363(1) Pages: 52-61
  • Peer Reviewed
• [Journal Article] エナメル質の横紋形成メカニズムの解明 (2012)
  • Author(s): 及川愛, 大津圭史, 藤原尚樹, 石関清人, 中富満城, 大島勇人, 原田英光
  • Journal Title: 岩医大歯誌 Volume: 37 Pages: 14-23
  • NAID: 110009445045
  • Peer Reviewed
• [Journal Article] Role of epithelial-stem cell interactions during dental cell differentiation (2012)
  • Author(s): Arakaki M, Ishikawa M, Nakamura T, Iwamoto T, Yamada A, Fukumoto E, Saito M, Otsu K, Harada H, Yamada Y, Fukumoto S
  • Journal Title: J Biol Chem Volume: 287(13) Pages: 10590-10601
  • Peer Reviewed
• [Journal Article] Osteogenic genes related to the canonic WNT pathway are down-regulated in ameloblastoma (2012)
  • Author(s): Sathi GA, Tsujigiwa H, Ito S, Siar CH, Katase N, Tamamura R, Harada H, Nagatsuka H
  • Journal Title: Oral Surg Oral Med Oral Pathol Oral Radiol Volume: 114(6) Pages: 771-7
  • Peer Reviewed
• [Journal Article] Promotional effects of vasoactive intestinal peptide on the development of rodent Hertwig's epithelial root sheath (2012)
  • Author(s): Xu J, Kawashima N, Fujiwara N, Harada H, Ota MS, Suda H
  • Journal Title: Congenit Anom (Kyoto) Volume: 52(3) Pages: 162-7
  • Peer Reviewed
• [Journal Article] 幹細胞(Stem Cell)研究がひらく歯の再生の扉 (2012)
  • Author(s): 大津圭史, 藤原尚樹, 原田英光
  • Journal Title: 日本歯科評論 Volume: 72(8) Pages: 9-11
• [Journal Article] iPS細胞から神経堤細胞への分化誘導法の確立 (2012)
  • Author(s): 大津圭史, 藤原尚樹, 原田英光
  • Journal Title: Dental Diamond Volume: 37(541) Pages: 92-95
• [Journal Article] Role of epithelial-stem cell interactions during dental cell differentiation (2012)
  • Author(s): Arakaki M, Ishikawa M, Nakamura T, Iwamoto T, Yamada A, Fukumoto E, Saito M, Otsu K, Harada H, Yamada Y, Fukumoto S
  • Journal Title: J Biol Chem Volume: 287(13) Issue: 13 Pages: 10590-601
  • DOI: 10.1074/jbc.m111.285874
  • Peer Reviewed
• [Journal Article] Hepatocyte growth factor stimulates root growth during the development of mouse molar teeth (2011)
  • Author(s): Sakuraba, H., Fujiwara, N., Sasaki-Oikawa, A., Sakano, M., Otsu, K., Ishizeki, K., Harada, H.
  • Journal Title: J.Period.Res. Volume: 47 Issue: 1 Pages: 81-88
  • DOI: 10.1111/j.1600-0765.2011.01407.x
  • Peer Reviewed
• [Presentation] エナメル上皮幹細胞研究から考えるヒトの歯の再生に向けた戦略と展望 (2013)
  • Author(s): 原田英光
  • Organizer: 第58回日本口腔外科学会総会・学術大会
  • Place of Presentation: 福岡
  • Year and Date: 2013-10-12
• [Presentation] ヒトの歯の再生に向けた戦略と展望 (2013)
  • Author(s): 原田英光
  • Organizer: 第11回日本再生歯科医学会総会・学術大会
  • Place of Presentation: 東京(日本大学松戸歯学部主催)
  • Year and Date: 2013-08-31
• [Presentation] Role of Rho signaling during amelogenesis. Tripartite Conference (Korea- Chaina- Japan) on Tooth and Bone; Development & Regeneration" in Seoul (2013)
  • Author(s): Harada, H., Otsu, K., Sakano, M., Fujiwara, N
  • Organizer: Korea will hold an International Symposium on "Tooth and Bone; Development & Regeneration"
  • Place of Presentation: Seoul, Korea
• [Presentation] イメージングを駆使した歯の発生の新たな理解への挑戦 (2013)
  • Author(s): 原田英光、大津圭史, 藤原尚樹, 坂野深香
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山
• [Presentation] Introduction-エナメル上皮幹細胞研究の国際的潮流と今後の展望 (2013)
  • Author(s): 原田英光 藤原尚樹 大津圭史
  • Organizer: 第118回日本解剖学会総会・全国学術集会
  • Place of Presentation: 高松(解剖学雑誌88(Suppl):100,2013)
• [Presentation] Sternness of dental epithelial stem cells considering feature of dental epithelial cells (2013)
  • Author(s): Harada, H., Otsu, K., Sakano, M., Fujiwara, N
  • Organizer: International Symposium Frontier Meeting, Seoul/Jeonju 2013 Development, Evolution, Taxonomy, and Genetics of Tooth Structure "Tooth Voyage, Up To Date"
  • Place of Presentation: Jeonju, Korea
• [Presentation] Cell dynamics in cervical loop epithelium during transition from crown to root : implications for Hertwig' epithelial root sheath formation (2013)
  • Author(s): Sakano, M, Otsu, K., Fujiwara, N., Harada, H
  • Organizer: International Symposium Frontier Meeting, Seoul/Jeonju 2013 Development, Evolution, Taxonomy, and Genetics of Tooth Structure "Tooth Voyage, Up To Date"
  • Place of Presentation: Jeonju, Korea
• [Presentation] AKTシグナルがグリコーゲン代謝を促進しエナメル芽細胞分化を誘導する (2013)
  • Author(s): 依田浩子, 大島勇人, 原田英光
  • Organizer: 第55回歯科基礎医学会学術大会・総会
  • Place of Presentation: 岡山(J Oral Biosci Suppl 2013,p.191,2013)
• [Presentation] イメージングを駆使した歯の発生の新たな理解への挑戦. (2013)
  • Author(s): 原田英光、大津圭史，藤原尚樹，坂野深香
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山
  • Invited
• [Presentation] Dental epithelial stemcells and tooth regeneration (2012)
  • Author(s): Hidemitsu Harada
  • Organizer: The 2012 International symposium, Dental and Cancer Stem cells
  • Place of Presentation: School of Dentistry, Seoul National University, Seoul, Korea
  • Year and Date: 2012-10-06
• [Presentation] 天然低分子化合物、ハルミンの歯根形成促進作用 (2012)
  • Author(s): 藤原尚樹、大津圭史、坂野深香、太田正人、原田英光
  • Organizer: 第54回歯科基礎医学会学術大会ならびに総会
  • Place of Presentation: 群山
  • Year and Date: 2012-09-16
• [Presentation] 口腔領域におけるiPS細胞研究の現状と展望 (2012)
  • Author(s): 原田英光、江草 宏
  • Organizer: 第54回歯科基礎医学会学術大会ならびに総会、サテライトシンポジウム3「口腔領域におけるips研究の現状と展望」
  • Place of Presentation: 群山
  • Year and Date: 2012-09-14
• [Presentation] iPS細胞から象牙芽細胞への分化誘導技術の開発と歯の再生への応用 (2012)
  • Author(s): 大津圭史
  • Organizer: 第54回歯科基礎医学会学術大会ならびに総会、サテライトシンポジウム3「口腔領域におけるips研究の現状と展望」
  • Place of Presentation: 群山
  • Year and Date: 2012-09-14
• [Presentation] 幹細胞成長因子による歯根形成の誘導 (2012)
  • Author(s): 藤原尚樹、坂野深香、大津圭史、原田英光
  • Organizer: 第54回歯科基礎医学会学術大会ならびに総会、サテライトシンポジウム3「口腔領域におけるips研究の現状と展望」
  • Place of Presentation: 群山
  • Year and Date: 2012-09-14
• [Presentation] 歯の発生・成長メカニズムから考える歯と歯周組織再生への展開 (2012)
  • Author(s): 原田英光
  • Organizer: 第28回東北矯正歯科学会大会
  • Place of Presentation: 仙台
  • Year and Date: 2012-05-20
• [Presentation] Adult stem cells versus iPS cells for human tooth regeneration (2012)
  • Author(s): Hidemitsu Harada, Keishi Otsu, NaokiFujiwara
  • Organizer: 2012 International Conference on Tooth and Bone Development and Regeneration
  • Place of Presentation: Chengdu, China
• [Presentation] iPS細胞から歯原性問葉細胞への分化誘導 (2012)
  • Author(s): 大津圭史, 藤原尚樹, 原田英光
  • Organizer: 第11回再生医療学会総会
  • Place of Presentation: 横浜
• [Presentation] ライブイメージングでとらえる歯の発生メカニズム (2012)
  • Author(s): 大津圭史, 原田英光
  • Organizer: 第117回日本解剖学会総会・全国学術大会研究集会・懇話会歯の発生の会シンポジウム
  • Place of Presentation: 山梨
• [Presentation] The role of Rho signaling pathway in dental epithelial stem cells (2012)
  • Author(s): Keishi Otsu, Hidemitsu Harada
  • Organizer: Gordon Research Conference, Craniofacial development an regenerative medicine
  • Place of Presentation: CA, U.S.A
• [Presentation] The role ofRho signaling pathway in dental epithelial stem cells (2012)
  • Author(s): Keishi Otsu, Ryota Kishigami, Al Oikawa-Sasaki, Naoki Fujiwara, Kiyoto Ishizeki, Hidemitsu Harada
  • Organizer: 117回 日本解剖学会総会・全国学術大会
  • Place of Presentation: 山梨
• [Presentation] Dental epithelial stem cells and tooth regeneration. (2012)
  • Author(s): Hidemitsu Harada
  • Organizer: The 2012 International symposium, Dental and Cancer Stem cells
  • Place of Presentation: Seoul National University, Seoul, Korea
  • Invited
• [Presentation] Adult stem cells versus iPS cells for human tooth regeneration (2012)
  • Author(s): Hidemitsu Harada, Keishi Otsu, Naoki Fujiwara
  • Organizer: 2012 International Conference on Tooth and Bone Development and Regeneration.
  • Place of Presentation: Chengdu, China
  • Invited
• [Book] Organ Cultures and Kidney-Capsule Grafting of tooth germs, Odontogenesis: Methods and Protocols (2012)
  • Author(s): Otsu,K., Fujiwara, N., Harada, H( (Eds; Chrissa Kioussi)
  • Publisher: Human Press SPRINGER SCIENCE
• [Remarks] 岩手医科大学解剖学講座発生生物再生医学分野
  • URL: http://oralhist.iwate-med.ac.jp/