New paradigm of enamel maturation: Mechanisms of non-endocytotic resorption and degradation of enamel matrix proteins

• Project/Area Number: 24390408
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: TAKANO Yoshiro 東京医科歯科大学, 医歯(薬)学総合研究科, 教授 (90126425)
• Co-Investigator(Kenkyū-buntansha): TABATA J Makoto 東京医科歯科大学, 大学院医歯学総合研究科, 准教授 (20243248) ; 馬場 麻人 東京医科歯科大学, 大学院・医歯学総合研究科, 助教 (90251545)
• Research Collaborator: ISEKI Hachiro
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥18,590,000 (Direct Cost: ¥14,300,000、Indirect Cost: ¥4,290,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2013: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000); Fiscal Year 2012: ¥12,480,000 (Direct Cost: ¥9,600,000、Indirect Cost: ¥2,880,000)
• Keywords: emamel matrix / amelogenin / proteasome / ubiquitin / endocytosis / ameloblast / enamel matrix / エナメル質 / 口腔解剖学 / 硬組織

Outline of Final Research Achievements

Massive removal of organic matrix components from immature enamel is essential for the induction of large apatite crystals and ultimately high mineralization of the unique dental tissue of epithelial origin.
Amelogenesis is characterized by degradation and re-absorption of enamel matrix proteins in both secretory and maturation stages of amelogenesis but how exactly the ameloblasts remove organic constituents is not well documented. Current study confirmed existence of organic anion transporters (OATs) in the Tomes’ process and ruffled border membranes of ameloblasts and that ameloblasts transport the cleavage product of enamel matrix proteins via OATs to the cytosol for final processing through the ubiquitin-proteasome system.

Research Products

• [Journal Article] Amelogenins as potential buffer during secretory-stage amelogenesis (2015)
  • Author(s): Guo J, Lyaruu D.M, Takano Y, Gibson CW, DenBesten PK and Bronckers ALJJ
  • Journal Title: Journal of Dental Research Volume: 94 Issue: 3 Pages: 412-420
  • DOI: 10.1177/0022034514564186
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Fluctuations in surface pH of maturing rat incisor enamel are a result of cycles of H+ secretion by ameloblasts and variations in enamel buffer characteristics (2014)
  • Author(s): Helle Damkier; Kaj Josephsen; Yoshiro Takano; Dirk Zahn; Ole Fejerskov; Sebastian
  • Journal Title: Bone Volume: 60 Pages: 227-234
  • DOI: 10.1016/j.bone.2013.12.018
  • Peer Reviewed
• [Journal Article] Fluorine in Shark Teeth: Its Direct Atomic-Resolution Imaging and Strengthening Function (2014)
  • Author(s): Chen, Chunlin; Wang, Zhongchang; Saito, Mitsuhiro; Tohei, Tetsuya; Takano, Yoshiro; Ikuhara, Yuichi
  • Journal Title: Angewandte Chemie Volume: 126 Issue: 6 Pages: 1569-1573
  • DOI: 10.1002/anie.201307689
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Tooth replacement and putative odontogenic stem cell niches in pharyngeal dentition of medaka (Oryzias latipes) (2014)
  • Author(s): Abduweli, D., O. Baba, M. J. Tabata, K. Higuchi, H. Mitani and Y. Takano
  • Journal Title: Microscopy (Oxf) Volume: 62(2) Issue: 2 Pages: 141-153
  • DOI: 10.1093/jmicro/dft085
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] In-vivo imaging of the fracture healing in medaka revealed two types of osteoclasts before and after the callus formation by osteoblasts (2014)
  • Author(s): Takeyama K, Chatani M, Takano Y, Kudo A
  • Journal Title: Developmental Biology Volume: 394(2) Issue: 2 Pages: 294-304
  • DOI: 10.1016/j.ydbio.2014.08.007
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Expression of transcripts for fibroblast growth factor 18 and its possible receptors during postnatal dentin formation in rat molars. (2014)
  • Author(s): Otto Baba. Masato S Ota, Tatsuo Terashima, Makoto J Tabata, Yoshiro Takano
  • Journal Title: Odontology Volume: 102 Issue: 2 Pages: 1-5
  • DOI: 10.1007/s10266-013-0147-9
  • Peer Reviewed
• [Journal Article] Alveolar bone loss induced by the orthodontic tooth movement under hypofunctional conditions in rats. (2013)
  • Author(s): Chisa Shitano, Otto Baba, Sawa Kaneko, Jun Hosomichi, Yasuhiro Shimizu, Naoki Shibutani,; Risa Usumi-Fujita, Yoshiro Takano, Takashi Ono
  • Journal Title: Orthodontic Waves Volume: 72 Issue: 4 Pages: 148-155
  • DOI: 10.1016/j.odw.2013.07.002
  • Peer Reviewed / Open Access
• [Journal Article] Organic Anion Transport in during Rat Enamel Formation (2013)
  • Author(s): A.R.K. Ratnayake, 他7名
  • Journal Title: Journal of Oral Bioscience Volume: 55 Pages: 40-46
  • Peer Reviewed
• [Presentation] メダカ咽頭歯の多換性とその維持機構 (2014)
  • Author(s): 高野吉郎
  • Organizer: 第56回歯科基礎医学会学術大会サテライトシンポジウム
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Rearing Medaka Fish in International Space Station (ISS) for Bone Metabolism Study (2014)
  • Author(s): Masahiro Chatani, Akiko Mantoku, Kazuhiro Takeyama, Kazuhiro Aoki, Yasutaka Sugamori, Keiichi Ohya, Satoko Uchida, Hiromi Suzuki, Toru Sakimura, Yasushi Kono, Fumiaki Tanigaki, Masaki Shirakawa, Keiji Inohaya, Dawud Abduweri, Yoshiro Takano, Akira Kudo
  • Organizer: ASBMR
  • Place of Presentation: Houston, USA
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] Imbalance of RANKL/OPG reveals the new bone resorption system with the whole-body analysis in medaka (2014)
  • Author(s): Masahiro Chatani, Yoshiro Takano, Takeshi Todo, Akira Kudo
  • Organizer: ASBMR
  • Place of Presentation: Houston, USA
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] 国際宇宙ステーションメダカ飼育実験による、微小重力における骨代謝の解 (2014)
  • Author(s): 茶谷昌宏、萬徳晃子、武山和弘、青木和広、大谷啓一、内田智子、鈴木ひろみ、崎村徹、河野靖、谷垣文章、白川正輝、猪早敬二、Dawud Abduweri、高野吉郎、工藤明
  • Organizer: 第３２回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] メダカを用いたRANKL/OPGＮバランス破壊による新たな全身骨吸収機構の解明 (2014)
  • Author(s): 茶谷昌宏、高野吉郎、藤堂剛、工藤明
  • Organizer: 第３２回日本骨代謝学会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2014-07-24 – 2014-07-26
• [Presentation] Involvement of organic anion trtansporters in non-endocytotic uptake of amelogenins during human tooth development (2014)
  • Author(s): C.K. Jayawardena, V. Walpola, T. Nandasena, D. Nanayakakara, and Y. Takano
  • Organizer: Peradeniya University International Research Session
  • Place of Presentation: Peradeniya, Sri Lanka
  • Year and Date: 2014-07-04 – 2014-07-05
• [Presentation] エナメル芽細胞のサイトゾルにおけるエナメルタンパク処理機構 (2014)
  • Author(s): 高野吉郎、井関八郎、杉浦真琴
  • Organizer: 日本顕微鏡学会第７０回学術大会
  • Place of Presentation: 幕張メッセ国際会議場
  • Year and Date: 2014-05-11 – 2014-05-13
• [Presentation] Fluctuations in Surface pH of Maturing Rat Incisor Enamel Are a Result of Cycles of H+-secretion by Ameloblasts and Variations in Enamel Buffer Characteristics (2014)
  • Author(s): Sebastian Frische, Helle Damkier, Kaj Josephsen, Yoshiro Takano, Dirk Zahn, Ole Fejerskov
  • Organizer: EB2014
  • Place of Presentation: San Diego, USA
  • Year and Date: 2014-04-26 – 2014-04-30
• [Presentation] Quantitative X-ray microprobe analysis of fluorotic amelogenin-null enamel (2014)
  • Author(s): Donacian M. Lyaruuｌ, Jing Guoｌ, Carolyn W. Gibson, Yoshiro Takano, Pamela DenBesten, Antonius LJJ Bronckers
  • Organizer: 11th International Conference on Tooth Morphogenesis and Differentiation
  • Place of Presentation: La Londo, France
• [Presentation] Cytosolic Processing of Enamel Matrix Proteins in Rat Incisors (2013)
  • Author(s): Yoshiro Takano, 他4名
  • Organizer: 第118回日本解剖学会全国学術集会
  • Place of Presentation: 高松国際会議場
  • Year and Date: 2013-03-30
• [Presentation] Co-Localization of Amelogenin and Ubiquitin/Proteasome in the Cytosol of Ameloblasts (2013)
  • Author(s): Yoshiro Takano, 他4名
  • Organizer: IADR/AADR/CADR 91^(st) General Session
  • Place of Presentation: Seattle Convention Center
  • Year and Date: 2013-03-23
• [Presentation] Cytosolic Processing of Enamel Matrix Proteins in Rat Incisors (2013)
  • Author(s): ChunLin Chen, 他4名
  • Organizer: 日本セラミックス協会2013年年会
  • Place of Presentation: 東京工業大学(大岡山キャンパス)
  • Year and Date: 2013-03-18
• [Presentation] Teleost Fish Medaka- A New Experimental Modal for Tooth Regeneration (2013)
  • Author(s): Dawud Abduweli, Otto Baba, Yoshiro Takano
  • Organizer: IADR-APR, JADR General Session 2013
  • Place of Presentation: Bangkok, Thailand
• [Presentation] Alveolar bone loss induced by hypofunctional tooth movement in rats. (2013)
  • Author(s): Chisa Shitano, Otto Baba, Sawa Kaneko, Jun Hosomichi, Yasuhiro Shimizu, Naoki Shibutani, Risa Usumi-Fujita, Yoshiro Takano, Takashi Ono
  • Organizer: IADR-APR, JADR General Session 2013
  • Place of Presentation: Bangkok, Thailand
• [Presentation] Atomic-Level Characterization of the Enameloid of Shark teeth (2013)
  • Author(s): ChunLin Chen, Mitsuhiro Saito, Zhongchang Wang, Tetsuya Tohei, Yoshiro Takano, Yuichi Ikuhara
  • Organizer: 日本顕微鏡学会第69回学術講演会
  • Place of Presentation: ホテル阪急エキスポパーク（吹田市）
• [Presentation] Propagating Waves of Ameloblast Modulation Affect Enamel pH, Mineral Acquisition, and Crystal Growth in Maturing Enamel (2013)
  • Author(s): Yoshiro Takano, Dawud Abduweli
  • Organizer: 日本顕微鏡学会第５７回シンポジウム
  • Place of Presentation: 愛知県産業労働センター（名古屋市）
• [Presentation] Organic Anion Transporters Play Roles in Human Enamel Formation (2012)
  • Author(s): C.K. JAYAWARDENA, 他4名
  • Organizer: 60th Annual Meeting of JADR
  • Place of Presentation: Niigata Convention Center
  • Year and Date: 2012-12-14
• [Presentation] Dynamic Events at the Cell-Matrix Interface in Amelogenesis : Contribution to Matrix Processing and Crystal Growth (2012)
  • Author(s): Yoshiro Takano
  • Organizer: 11th Annual Meeting of Korean Basic Dental Science Societies Association
  • Place of Presentation: Korea, Kyung Hee Univ.
  • Year and Date: 2012-11-23
• [Presentation] Organic Anion Transporters in Rat Enamel Formation (2012)
  • Author(s): R.A.R.K. Ratnayake, 他2名
  • Organizer: 第100回日本解剖学会関東支部学術集会
  • Place of Presentation: 大田区Toho-University
  • Year and Date: 2012-10-13
• [Presentation] レトロウイルスベクターによる歯根膜細胞由来のiPS細胞の樹立とその安全性の検討 (2012)
  • Author(s): 花田信弘, 他9名
  • Organizer: 第54回歯科基礎医学会学術大会
  • Place of Presentation: 郡山市 奥羽大学歯学部
  • Year and Date: 2012-09-15
• [Presentation] Cell and Matrix Regulation of Amelogenesis (2012)
  • Author(s): Yoshiro Takano
  • Organizer: Kyung Hee University Graduate School Seminar
  • Place of Presentation: Seoul, Kyung Hee University
  • Year and Date: 2012-09-11
• [Presentation] エナメル質成熟化に伴う巨大アパタイト結晶誘導機構解明への微細構造学的アプローチ (2012)
  • Author(s): 高野吉郎
  • Organizer: 日本顕微鏡学会第68回学術講演会
  • Place of Presentation: つくば市国際会議場
  • Year and Date: 2012-05-14
• [Presentation] Ameloblast cell modulation during enamel maturation – why and how?
  • Author(s): Yoshiro Takano
  • Organizer: Ole Fejerskov Memorial Symposium, Oral Biology 1967-2013
  • Place of Presentation: Aarhus, Denmark
  • Invited
• [Presentation] 硬組織の形成と石灰化の制御機構
  • Author(s): 高野吉郎
  • Organizer: 鶴見大学歯学部歯科矯正科・鶴見大学歯学会・歯学研究科ＦＤ委員会共催講演会
  • Place of Presentation: 鶴見大学（横浜市）
• [Presentation] エナメル質成熟化の仕組み ー巨大アパタイト結晶誘導の細胞性制御ー
  • Author(s): 高野吉郎
  • Organizer: 松本歯科大学大学院セミナー
  • Place of Presentation: 松本歯科大学（塩尻市）
• [Book] Newton別冊人体はなにで作られているのか (2013)
  • Author(s): 高野吉郎
  • Total Pages: 160
  • Publisher: ニュートンプレス