The development of novel drug promoting dentin formation by odontoblast intercellular signal transduction factors (ATP/glutamate)
Project/Area Number |
15K11129
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Conservative dentistry
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Research Institution | Tokyo Dental College |
Principal Investigator |
Kimura Maki 東京歯科大学, 歯学部, 講師 (90582346)
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Co-Investigator(Kenkyū-buntansha) |
渋川 義幸 東京歯科大学, 歯学部, 教授 (30276969)
田崎 雅和 東京歯科大学, 歯学部, 教授 (40155065)
佐藤 正樹 東京歯科大学, 歯学部, 講師 (80598855)
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Research Collaborator |
KOJIMA yuki
HIGASHIKAWA asuka
NISHIYAMA akihiro
SHIOZAKI yuta
SATOU ryouichi
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Project Period (FY) |
2015-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | 象牙芽細胞 / アルカリ / 石灰化 / アルカリ刺激 / SOCE |
Outline of Final Research Achievements |
In the present research project, results obtained by mineralization assay are as follows: 1) Alkaline stimuli to the human odontoblasts increased their mineralization levels, 2) TRPA1 channels mediated mineralization mechanism under both extracellular physiologic and high pH conditions in the odontoblasts. In the intracellular Ca2+ concentration measurements, we obtained following results: 1) Odontoblasts expressed store-operated Ca2+ entry (SOCE) via an activation of Ca2+ release-activated Ca2+ channels, 2) Activation of P2Y or muscarinic cholinergic receptors induced SOCE in odontoblasts, 3) Alkaline stimuli increased the amplitude of SOCE in odontoblasts.
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Academic Significance and Societal Importance of the Research Achievements |
本研究で、アルカリ刺激により象牙芽細胞に生じるCa2+シグナルとそのCa2+シグナルの結果放出された象牙芽細胞間連絡因子が近傍象牙芽細胞に誘発させるCa2+シグナルを明らかにした。この成果の学術的意義は、歯科臨床で多用される水酸化カルシウム製剤・MTAなどの高Ca 含有アルカリ性製剤の象牙質形成促進作用メカニズムの一端を解明したことである。本研究成果の社会的意義はより象牙質形成速度の速い新規高Ca含有アルカリ性製剤の開発につながることである。
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Report
(5 results)
Research Products
(72 results)
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[Journal Article] Odontoblasts as sensory receptors: transient receptor potential channels, pannexin-1, and ionotropic ATP receptors mediate intercellular odontoblast-neuron signal transduction2015
Author(s)
Shibukawa, Y., Sato, M., Kimura, M., Sobhan, U., Shimada, M., Nishiyama, A., Kawaguchi, A., Soya, M., Kuroda, H., Katakura, A., Ichinohe, T., and Tazaki, M.
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Journal Title
Pflügers Archiv European Journal of Physiology
Volume: 467
Issue: 4
Pages: 843-863
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Depolarization-induced Intracellular Free Calcium Concentration Increases Show No Desensitizing Effect in Rat Odontoblasts2015
Author(s)
Kojima Y, Higashikawa A, Kimura M, Sato M, Mochizuki H, Ogura K, Sase T, Shinya A, Kobune K, Furuya T, Sato T, Shibukawa Y, Tazaki M
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Journal Title
The Bulletin of Tokyo Dental College
Volume: 56
Issue: 2
Pages: 131-134
DOI
NAID
ISSN
0040-8891
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Transient Receptor Potential Cation Channel Subfamily Vanilloid Member 3 is not Involved in Plasma Membrane Stretch-induced Intracellular Calcium Signaling in Merkel Cells2015
Author(s)
Higashikawa A, Kojima Y, Sato M, Kimura M, Ogura K, Mochizuki H, Sase T, Shinya A, Kobune K, Furuya T, Sato T, Shibukawa Y, Tazaki M.
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Journal Title
The Bulletin of Tokyo Dental College
Volume: 56
Issue: 4
Pages: 259-262
DOI
NAID
ISSN
0040-8891
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Presentation] Intracellular cAMP induces Ca2+ influx in odontoblasts2019
Author(s)
Maki Kimura, Asuka Higashikawa, Sadao Ohyama, Wataru Ofusa, Miyuki Shimada, Hidetaka Kuroda, Hiroyuki Mochizuki, Masayuki Ando, Kyosuke Kono, Yoshiyuki Shibukawa
Organizer
9th Federation of the Asian and Oceanian Physiological Societies congress (FAOPS), 第96回日本生理学会大会
Related Report
Int'l Joint Research
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[Presentation] Direct Mechanical stimulation evoked Gd3+-sensitive inward current in trigeminal ganglion neurons2019
Author(s)
Asuka Higashikawa, Maki Kimura, Miyuki Shimada, Hidetaka Kuroda, Wataru Ofusa, Sadao Ohyama, Masayuki Ando, Kyousuke Kono, Hiroyuki Mochizuki, Yoshiyuki Shibukawa
Organizer
9th Federation of the Asian and Oceanian Physiological Societies congress (FAOPS), 第96回日本生理学会大会
Related Report
Int'l Joint Research
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[Presentation] Odontoblasts express plasma membrane Ca2+-ATPase 1 and 42018
Author(s)
Kimura Maki, Higashikawa Asuka, Kojima Yuki, Terashima-Shigefuji Reiko, Inoue Hiroyuki, Nagai Sayoko, Kamata Satomi, Shimada Miyuki, Kuroda Hidetaka, Ogura Kazuhiro, Mochizuki Hiroyuki, Kouno Kyosuke, Ando Masayuki, Shibukawa Yoshiyuki, Tazaki Masakazu
Organizer
第95回日本生理学会大会
Related Report
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[Presentation] Alkali- and ADP-sensitive store-operated Ca2+ entry (SOCE) mediated by Ca2+ release-activated Ca2+ (CRAC) channels in rat odontoblasts2017
Author(s)
Maki Kimura, Masaki Sato, Yuki Kojima, Asuka Higashikawa, Yuuta Shiozaki, Ryoichi Satou, Reiko Shigefuji, Miyuki Shimada, Hidetaka Kuroda, Kazuhiro Ogura, Hiroyuki Mochizuki, Kyosuke Kouno, Yoshiyuki Shibukawa, Masakazu Tazaki
Organizer
第94回日本生理学会大会
Place of Presentation
第94回日本生理学会大会
Year and Date
2017-03-28
Related Report
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[Presentation] High pH-sensitive TRPA1 channel activation acts as a key Ca2+ signaling that regulates dentin mineralization by odontoblasts2016
Author(s)
Maki Kimura, Masaki Sato, Yuki Kojima, Asuka Higashikawa, Miyuki Shimada, Yuuta Shiozaki, Ryoichi Satou, Reiko Shigefuji, Kazuhiro Ogura, Hiroyuki Mochizuki, Kyosuke Kouno, Yoshiyuki Shibukawa, Masakazu Tazaki
Organizer
International Association of Dental Research (IADR) Pulp Biology and Regeneration Group (PBRG) Symposium 2016
Place of Presentation
Nagoya, Japan
Year and Date
2016-06-26
Related Report
Int'l Joint Research
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[Presentation] Store-operated Ca2+ entry in rat odontoblasts2016
Author(s)
Maki Kimura, Asuka Higashikawa (presenter), Masaki Sato, Yuki Kojima, Miyuki Shimada, Yuuta Shiozaki, Ryoichi Satou, Reiko Shigefuji, Kazuhiro Ogura, Hiroyuki Mochizuki, Kyosuke Kouno, Yoshiyuki Shibukawa, Masakazu Tazaki
Organizer
International Association of Dental Research (IADR) Pulp Biology and Regeneration Group (PBRG) Symposium 2016
Place of Presentation
Nagoya, Japan
Year and Date
2016-06-26
Related Report
Int'l Joint Research
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[Presentation] Odontoblasts as sensory receptors: Transient receptor potential channels, pannexin-1 and ionotropic ATP receptors, mediate intracellular odontoblast-trigeminal ganglion neuron signal transduction2016
Author(s)
oshiyuki Shibukawa, Masaki Sato, Maki Kimura, Ubaidus Sobhan, Yuki Kojima, Asuka Higashikawa, Yuuta Shiozaki, Ryoichi Satou, Reiko Shigefuji, Miyuki Shimada, Kazuhiro Ogura, Hiroyuki Mochizuki, Kyosuke Kouno, Masakazu Tazaki
Organizer
International Association of Dental Research (IADR) Pulp Biology and Regeneration Group (PBRG) Symposium 2016
Place of Presentation
Nagoya, Japan
Year and Date
2016-06-26
Related Report
Int'l Joint Research
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[Presentation] ATP released from odontoblasts by mechanosensitive TRP and piezo channel activations generates P2X3-mediated action potentials in trigeminal ganglion neurons2016
Author(s)
Masaki Sato, Maki Kimura, Yuki Kojima, Asuka Higashikawa, Yuuta Shiozaki, Ryoichi Satou, Reiko Shigefuji, Miyuki Shimada, Kazuhiro Ogura, Hiroyuki Mochizuki, Kyosuke Kouno, Masakazu Tazaki, Yoshiyuki Shibukawa
Organizer
International Association of Dental Research (IADR) Pulp Biology and Regeneration Group (PBRG) Symposium 2016
Place of Presentation
Nagoya, Japan
Year and Date
2016-06-26
Related Report
Int'l Joint Research
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[Presentation] Biophysical properties of a Voltage-dependent K+ current in odontoblasts2016
Author(s)
Yuki Kojima, Asuka Higashikawa, Maki Kimura, Masaki Sato, Yuuta Shiozaki, Ryoichi Satou, Reiko Shigefuji, Miyuki Shimada, Kazuhiro Ogura, Hiroyuki Mochizuki, Kyosuke Kouno, Yoshiyuki Shibukawa, Masakazu Tazaki
Organizer
International Association of Dental Research (IADR) Pulp Biology and Regeneration Group (PBRG) Symposium 2016
Place of Presentation
Nagoya, Japan
Year and Date
2016-06-26
Related Report
Int'l Joint Research
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[Presentation] High pH-sensitive TRPA1 channel activation in odontoblasts regulates dentin mineralization and calcification2016
Author(s)
Kimura M, Shibukawa Y, Sato M, Kojima Y, Higashikawa A, Kouno K, Shimada M, Mochizuki H, Ogura K, Tazaki M
Organizer
12th International Confference on Tooth Morphogenesis and Differentiation
Place of Presentation
Porvoo, Finland
Year and Date
2016-06-13
Related Report
Int'l Joint Research
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[Presentation] Expression of store-operated Ca2+ entry (SOCE) mediated by Ca2+ release-activated Ca2+ (CRAC) channels in rat odontoblasts2016
Author(s)
Kimura M, Sato M, Kojima Y, Higashikawa A, Shiozaki Y, Satou R, Shigefuji R, Shimada M, Kobune K, Ogura K, Mochizuki H, Kouno K, Shibukawa Y, Tazaki M
Organizer
第93回日本生理学会大会
Place of Presentation
札幌市
Year and Date
2016-03-22
Related Report
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[Presentation] Evoked inward currents in trigeminal ganglion neurons caused by intracellular transmitters, ATP, released from mechanically stimulated odontoblasts2016
Author(s)
Sato M, Kobune K, Kimura M, Kojima Y, Higashikawa A, Ogura K, Mochizuki H, Kouno K, Shimada M, Shibukawa Y, Tazaki M.
Organizer
第93回日本生理学会大会
Place of Presentation
札幌市
Year and Date
2016-03-22
Related Report
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[Presentation] Activated mechanisms of H+-sensing ionotropic receptors and G-protein-coupled H+-sensing receptors in odontoblasts2015
Author(s)
Sato M, Kurasawa K, Okabayashi K, Kimura M, Kojima Y, Higashikawa A, Shimada M, Ogura K, Mochizuki H, Sase T, Shinya A, Kobune K, Shibukawa Y and Tazaki M
Organizer
JOINT RESEARCH PROJECT (JSPS) UNDER THE JAPAN-KOREA BASIC SCIENTIFIC COOPERATION PROGRAM FOR FY 2015
Place of Presentation
成田市
Year and Date
2015-06-12
Related Report
Invited
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[Presentation] Alkaline-sensitive intracellular Ca2+ signaling pathway in rat odontoblasts2015
Author(s)
Kimura M, Sato M, Kojima Y, Higashikawa A, Nishiyama A, Satou R, Shiozaki Y, Shimada M, Ogura K,Mochizuki H, Sase T, Shinya A, Kobune K, Furuya T, Sato T, Shibukawa Y, Tazaki M
Organizer
JOINT RESEARCH PROJECT (JSPS) UNDER THE JAPAN-KOREA BASIC SCIENTIFIC COOPERATION PROGRAM FOR FY 2015
Place of Presentation
成田市
Year and Date
2015-06-12
Related Report
Invited
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