Vitamin D regulates dental epithelial cell differentiation and enamel formation

• Project/Area Number: 15K15752
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: Nakamura Takashi 東北大学, 歯学研究科, 准教授 (90585324)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: エナメル / ビタミンD / ビタミンＤ欠乏症 / 25OHD3 / 歯原性上皮細胞 / 紫外線 / 1,25(OH)2D3 / エナメル形成不全 / 妊婦 / MIH / エナメル質形成不全 / くる病 / エナメル低石灰化症 / 永久歯 / カルシウム / 器官培養 / 日光 / 石灰化機構

Outline of Final Research Achievements

The aim of this research is to elucidate the mechanism of vitamin D during enamel formation as well as enamel mineralization. 1,25(OH)2D3 promoted the expression of a series of enamel matrix proteins such as Ameloblastin, enamelin, and amelogenin in dental epithelial cells. Thus, 1,25(OH)2D3 promotes dental epithelial cell differentiation into ameloblast. In addition, long term culture of dental epithelial cells in the presence of 10-7M 1,25(OH)2D3 with mineralization media induced the mineralization of culture cells as well as secreted matrices. Attrition of the tip of incisors and molars are observed in rats which feed vitamin D-deficient diet for 12 weeks. Furthermore, incisors of vitamin D-deficient rats showed chalky white enamel suggesting enamel hypomineralization. These results suggest that 1,25(OH)2D3 is an essential vitamin for normal enamel formation.

Research Products

• [Int'l Joint Research] NIDCR, NIH/The Children's Hospital of Philadelphia(米国)
• [Int'l Joint Research] University of the Basque County(Spain)
• [Int'l Joint Research] Peking University(China)
• [Journal Article] Epiprofin Regulates Enamel Formation and Tooth Morphogenesis by Controlling Epithelial-Mesenchymal Interactions During Tooth Development. (2017)
  • Author(s): Nakamura T, Jimenez-Rojo L, Koyama E, Pacifici M, de Vega S, Iwamoto M, Fukumoto S, Unda F, Yamada Y.
  • Journal Title: J Bone Miner Res. Volume: 32 Issue: 3 Pages: 601-610
  • DOI: 10.1002/jbmr.3024
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Pannexin 3 regulates proliferation and differentiation of odontoblasts via its hemichannel activities (2017)
  • Author(s): Iwamoto Tsutomu、Nakamura Takashi、Ishikawa Masaki、Yoshizaki Keigo、Sugimoto Asuna、Ida-Yonemochi Hiroko、Ohshima Hayato、Saito Masahiro、Yamada Yoshihiko、Fukumoto Satoshi
  • Journal Title: PLOS ONE Volume: 12 Issue: 5 Pages: 0177557-0177557
  • DOI: 10.1371/journal.pone.0177557
  • NAID: 120006534958
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Globoside accelerates the differentiation of dental epithelial cells into ameloblasts (2016)
  • Author(s): Nakamura, T., Chiba, Y., Naruse, M., Harada, H., and Fukumoto, S.
  • Journal Title: Intenational Journal of Oral Science Volume: 8(4) Issue: 4 Pages: 205-212
  • DOI: 10.1038/ijos.2016.35
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Connexin 43 is necessary for salivary gland branching morphogenesis and FGF10-induced ERK1/2 phosphorylation (2016)
  • Author(s): Yamada A, Futagi M, Fukumoto E, Saito K, Yoshizaki K, Ishikawa M, Arakaki M, Hino R, Sugawara Y, Ishikawa M, Naruse M, Miyazaki K, Nakamura T, Fukumoto S.
  • Journal Title: The Journal of Biological Chemistry Volume: 291 Issue: 2 Pages: 904-912
  • DOI: 10.1074/jbc.m115.674663
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mutant GDF5 enhances ameloblast differentiation via accelerated BMP2-induced Smad1/5/8 phosphorylation (2016)
  • Author(s): Liu J, Saito K*, Maruya Y, Nakamura T, Yamada A, Fukumoto E, Ishikawa M, Iwamoto T, Miyazaki K, Yoshizaki K, Ge L, Fukumoto S
  • Journal Title: Scientific reports Volume: 6 Issue: 1 Pages: 23670-23670
  • DOI: 10.1038/srep23670
  • NAID: 120006534957
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Wnt3a signaling induces murine dental follicle cells to differentiate into cementoblastic/osteoblastic cells via an osterix-dependent pathway. (2015)
  • Author(s): Nemoto, E., Sakisaka, M., Tsuchiya, M., Tamura, M., Nakamura, T., Shimonishi, M., and Shimauchi
  • Journal Title: Journal of Periodontal Research Volume: 51(2) Issue: 2 Pages: 164-174
  • DOI: 10.1111/jre.12294
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Wnt5a attenuates canonical Wnt-induced alkaline phosphatase expression in dental follicle cells. (2015)
  • Author(s): Sakisaka, Y., Tsuchiya, M., Nakamura, T., Tamura, M., Shimauchi, H., and Nemoto, E.
  • Journal Title: Experimental Cell Research Volume: 336(1) Issue: 1 Pages: 85-93
  • DOI: 10.1016/j.yexcr.2015.06.013
  • Peer Reviewed
• [Journal Article] Articular cartilage endurance and resistance to osteoarthritic changes require transcription factor Erg. (2015)
  • Author(s): Ohta, Y., Okabe, T., Larmoura, C., Di Roccoa, A., Maijenburg, M., Phillips, A., Speck, NA., Wakitani, S., Nakamura, T., Yamada, Y., Enomoto-Iwamoto, M., Pacifici, M., and Iwamoto, M.
  • Journal Title: Arthritis & Rheumatology Volume: 67(10) Issue: 10 Pages: 2679-2690
  • DOI: 10.1002/art.39243
  • Peer Reviewed
• [Presentation] Zn2+ Hyperpolarizes Osteoblastic MC3T3-E1 Cells by Activating IK and BK Channels (2017)
  • Author(s): Mengkai Guang, Takashi Yoshida, Takashi Nakamura, Ping Gong, Minoru Wakamori
  • Organizer: 95th General Session & Exhibition of the IADR
  • Place of Presentation: San Francisco, CA USA
  • Year and Date: 2017-03-22
  • Int'l Joint Research
• [Presentation] エピプロフィンによる骨代謝調節 (2016)
  • Author(s): 中村 卓史，中村 友昭，若森 実，福本 敏
  • Organizer: 第58回歯科基礎医学会学術大会
  • Place of Presentation: 札幌
  • Year and Date: 2016-08-24
• [Book] 日本抗加齢医学会雑誌 (2015)
  • Author(s): 福本 敏、新垣真紀子、山田亜矢、齋藤 幹、中村卓史
  • Total Pages: 7
  • Publisher: メディカルビュー社
• [Book] エナメル芽細胞の分化制御機構 (2015)
  • Author(s): 中村卓史
  • Total Pages: 11
  • Publisher: 臨床医学出版