Biological synthesis of phosphate ions and its feedback mechanism of osteocyte

• Project/Area Number: 15H05010
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Hokkaido University
• Principal Investigator: AMIZUKA Norio 北海道大学, 歯学研究院, 教授 (30242431)
• Co-Investigator(Renkei-kenkyūsha): ODA Kimimitsu 新潟大学, 医歯学総合研究科, 教授 (10122681)
• Research Collaborator: HASEGAWA Tomoka ; HONGO Hiromi ; YAMAMOTO Tomomaya
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2015: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
• Keywords: 骨細胞 / 石灰化 / FGF23 / ENPP1 / TNAP / 骨代謝 / 歯槽骨 / klotho / kl/klマウス / αklotho-/-マウス

Outline of Final Research Achievements

αKlotho-/-mice and kl/kl mice prevented the increment of serum phosphate level, when being fed with low-phosphate diets. Low-phosphate diets rescued the reduced mineralization of kl/kl bone but not αklotho-/-bone, indicating that bone mineralization seems to be regulated not only by serum concentration of phosphate, but also other mechanism. In a normal state, steoblasts being about to differentiate into osteocytes localized podoplanin and phsophorylated-ezrin along the cell membranes. ENPP1-/-mice and kl/kl mice prematurely demonstrated many osteoblasts featuring podoplanin and phosphorylated-ezrin. Therefore, the elevated concentration of serum phosphate and/or membrane transporters/enzymes serving for phosphate ion-supplement may be involved in osteocytic differentiation from osteoblasts.

Research Products

• [Journal Article] Characterization of a PTH1R missense mutation responsible for Jansen type metaphyseal chondrodysplasia. (2017)
  • Author(s): Shimomura-Kuroki J, Farooq M, Sekimoto T, Amizuka N, Shimomura Y.
  • Journal Title: Odontology Volume: 105 Issue: 2 Pages: 150-154
  • DOI: 10.1007/s10266-016-0247-4
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histochemical examination on periodontal tissues of Klotho-deficient mice fed with phosphate insufficient diet. (2017)
  • Author(s): Hikone K., Hasegawa T., Tsuchiya E., Hongo H., Sasaki M., Yamamoto T., Kudo A., Oda K., Haraguchi M., Freitas PHL., Li M., Iida J., Amizuka N.
  • Journal Title: The Journal of Histochemistry and Cytochemistry Volume: 65巻4号 Issue: 4 Pages: 207-221
  • DOI: 10.1369/0022155416689670
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] <b>Histochemical assessment for osteoblastic activity coupled with dysfunctional osteoclasts in </b><i><b>c-src</b></i><b> deficient </b><b>mice </b> (2017)
  • Author(s): Toraya H., Hasegawa T., Sakagami N., Tsuchiya E., Kudo A., Zhao S., Moritani Y., Abe M., Yoshida T., Yamamoto T., Yamamoto T., Oda K., Udagawa N., Freitas PHL., Li M., Amizuka N.
  • Journal Title: Biomedical Research Volume: 38 Issue: 2 Pages: 123-134
  • DOI: 10.2220/biomedres.38.123
  • NAID: 130005606444
  • ISSN: 0388-6107, 1880-313X
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ultrastructural and biochemical aspects of matrix vesicle-mediated mineralization. (2017)
  • Author(s): Hasegawa T., Yamamoto T., Tsuchiya E., Hongo H., Tsuboi K., Kudo A., Abe M., Yoshida T., Nagai T., Khadiza N., Yokoyama A., Oda K., Ozawa H., Freitas de PHL., Li M., Amizuka N.
  • Journal Title: Japanese Dental Science Review Volume: 53巻2号 Issue: 2 Pages: 34-45
  • DOI: 10.1016/j.jdsr.2016.09.002
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Cellular function of osteocytes in normal and αklotho-deficient mice. (2017)
  • Author(s): Amizuka N., Hasegawa T., Yamamoto T., Mae T., Qiu Z., Kudo A., Abe M., Zhao S., Nagai T., Yokoyama A., Khadiza N., Haraguchi M., Yamamoto T., de Freitas PHL., Li M.
  • Journal Title: Hokkaido of Dent Sci. Volume: 38(Special issue) Pages: 56-62
  • NAID: 120006360110
  • Int'l Joint Research
• [Journal Article] Effects of drug discontinuation after short-term daily alendronate administration on osteoblasts and osteocytes. (2016)
  • Author(s): Tsuboi K., Hasegawa T., Yamamoto T., Sasaki M., Hongo H., Oda K., Michigami T., Li M., Freitas PHL., Kitagawa Y., Amizuka N.
  • Journal Title: Histochemistry and Cell Biology Volume: 146巻3号 Issue: 3 Pages: 337-350
  • DOI: 10.1007/s00418-016-1450-7
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Localization of minodronate in mouse femora through isotope microscopy. (2016)
  • Author(s): Hongo, H., Sasaki, M., Kobayashi, S., Hasegawa, T., Yamamoto, T., Tsuboi, K., Tsuchiya, E., Nagai, T., Khadiza, N., Abe, M., Kudo, A., Oda, K., Henrique Luiz de Freitas, P., Li, M., Yurimoto, H. and Amizuka, N.
  • Journal Title: Journal of Histochemistry & Cytochemistry Volume: 64 Issue: 10 Pages: 601-622
  • DOI: 10.1369/0022155416665577
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histological assessment for femora of ovariectomized obesity (db/db) mice carrying mutated leptin receptor. (2016)
  • Author(s): Tanaka Y, Hasegawa T, Yamada T, Yamamoto T, Sasaki M, Hongo H, Tsuboi K, Haraguchi M, de Freitas PH, Li M, Oda K, Totsuka Y, Tei K, Amizuka N.
  • Journal Title: HISTOLOGY AND HISTOPATHOLOGY Volume: 印刷中
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Calcilytic Ameliorates Abnormalities of Mutant Calcium-Sensing Receptor (CaSR) Knock-In Mice Mimicking Autosomal Dominant Hypocalcemia (ADH). (2015)
  • Author(s): Dong B, Endo I, Ohnishi Y, Kondo T, Hasegawa T, Amizuka N, Kiyonari H, Shioi G, Abe M, Fukumoto S, Matsumoto T.
  • Journal Title: Journal of bone and mineral research Volume: 30 Issue: 11 Pages: 1980-1993
  • DOI: 10.1002/jbmr.2551
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Expression of matrix Gla protein and osteocalcin in the developing tibial epiphysis of mice. (2015)
  • Author(s): Liu H, Guo J, Wei S, Lv S, Feng W, Cui J, Hasegawa T, Hongo H, Yang Y, Li X, Oda K, Amizuka N, Li M.
  • Journal Title: HISTOLOGY AND HISTOPATHOLOGY Volume: 30 Pages: 77-85
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 骨基質石灰化におけるリン-FGF23-Klotho axis (2018)
  • Author(s): 網塚憲生
  • Organizer: 第63回日本透析医学会学術集会・総会
  • Invited
• [Presentation] PTH間歇投与マウスの骨組織におけるリン酸イオン供与膜輸送体・酵素群の局在． (2018)
  • Author(s): 前 壮功仁、山本知真也、趙 申、邱 紫セン、長谷川智香、山崎 裕、網塚憲生
  • Organizer: 第123回日本解剖学会総会・全国学術集会
• [Presentation] Fgf23遺伝子欠損マウスの骨基質石灰化異常におけるSIBLING familyの関与． (2018)
  • Author(s): 長谷川智香、邱 紫セン、山本知真也、本郷裕美、松井 功、網塚憲生
  • Organizer: 第38回日本骨形態計測学会
• [Presentation] Fgf23遺伝子欠損マウスの骨基質石灰化異常におけるSIBLING familyの局所作用． (2018)
  • Author(s): 長谷川智香、邱 紫セン、山本知真也、本郷裕美、松井 功、網塚憲生
  • Organizer: 第36回日本骨代謝学会
• [Presentation] 骨質に影響を及ぼす骨の微細構造と細胞群の役割． (2017)
  • Author(s): 網塚憲生、長谷川智香
  • Organizer: 第16回日本再生医療学会総会
  • Place of Presentation: 仙台国際センター(宮城県仙台市)
  • Year and Date: 2017-03-07
  • Invited
• [Presentation] 骨の細胞に対するPTH作用の組織学的知見． (2017)
  • Author(s): 網塚憲生、長谷川智香
  • Organizer: 第62回日本透析医学会学術集会・総会
  • Invited
• [Presentation] 骨芽細胞から骨細胞へ：微細構造学的知見． (2017)
  • Author(s): 長谷川智香、永井伯弥、本郷裕美、網塚憲生
  • Organizer: 第59回歯科基礎医学会学術大会
  • Invited
• [Presentation] 骨基質石灰化における局所リン酸供与とFGF23/klothoシグナル． (2017)
  • Author(s): 長谷川智香、本郷裕美、網塚憲生
  • Organizer: 第59回歯科基礎医学会学術大会
  • Invited
• [Presentation] aklotho/FGF23破綻による骨組織石灰化異常は低リン食給餌により回復する． (2017)
  • Author(s): 長谷川智香、網塚憲生
  • Organizer: 第37回日本骨形態計測学会
• [Presentation] kl/klマウスにおける基質小胞性石灰化の抑制メカニズムについて． (2017)
  • Author(s): 長谷川智香、山本知真也、網塚憲生
  • Organizer: 第35回日本骨代謝学会学術集会
• [Presentation] 骨芽細胞から骨細胞へのスイッチングにおけるpodoplaninの局在． (2017)
  • Author(s): 永井伯弥、長谷川智香、横山敦郎、網塚憲生
  • Organizer: 日本解剖学会第63回東北・北海道連合支部学術集会
• [Presentation] 骨粗鬆症治療薬における骨の細胞・組織学的知見について －動物モデルを用いた基礎研究－． (2016)
  • Author(s): 網塚憲生
  • Organizer: 第31回日本整形外科学会基礎学術集会
  • Place of Presentation: 福岡国際会議場(福岡県福岡市)
  • Year and Date: 2016-10-13
  • Invited
• [Presentation] 骨基質石灰化異常における微細構造学的知見． (2016)
  • Author(s): 網塚憲生、長谷川智香
  • Organizer: 第36回日本骨形態計測学会
  • Place of Presentation: 朱鷺メッセ 新潟コンベンションセンター(新潟県新潟市)
  • Year and Date: 2016-06-23
  • Invited
• [Presentation] Overview：骨基質石灰化における微細構造学． (2016)
  • Author(s): 網塚憲生、長谷川智香、本郷裕美
  • Organizer: 第121回日本解剖学会総会全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] FGF23/klotho軸破綻による骨・血管の石灰化異常． (2016)
  • Author(s): 長谷川智香、佐々木宗輝、山本知真也、本郷裕美、坪井香奈子、網塚憲生
  • Organizer: 第121回日本解剖学会総会全国学術集会
  • Place of Presentation: ビッグパレットふくしま（福島県郡山市）
  • Year and Date: 2016-03-28
  • Invited
• [Presentation] FIB-SEM を用いた骨組織の微細構造解析． (2015)
  • Author(s): 網塚憲生、長谷川智香
  • Organizer: 日本顕微鏡学会第71回学術講演会
  • Place of Presentation: 国立京都国際会館(京都府京都市)
  • Year and Date: 2015-05-13
  • Invited
• [Presentation] Histological aspects on the biological function of osteocytes. (2015)
  • Author(s): Amizuka N., Hasegawa T., Hongo H., Yamamoto T.
  • Organizer: 13th Congress of the International Society of Bone Morphometry
  • Place of Presentation: パレスホテル東京(東京都千代田区)
  • Year and Date: 2015-04-27
  • Int'l Joint Research / Invited
• [Book] CKD-MBD 3rd Edition (2018)
  • Author(s): 網塚憲生、邱 紫セン、長谷川智香
  • Publisher: 株式会社日本メディカルセンター
• [Book] 新骨の科学 (2016)
  • Author(s): 網塚憲生
  • Publisher: 医歯薬出版株式会社
• [Book] 骨ペディア 骨疾患・骨代謝キーワード事典 (2015)
  • Author(s): 網塚憲生、長谷川智香
  • Total Pages: 328
  • Publisher: 羊土社
• [Book] 口腔組織・発生学 第２版 (2015)
  • Author(s): 網塚憲生、笹野泰之
  • Total Pages: 384
  • Publisher: 医歯薬出版株式会社
• [Book] 口腔組織・発生学 第２版 (2015)
  • Author(s): 網塚憲生
  • Total Pages: 384
  • Publisher: 医歯薬出版株式会社
• [Remarks] 北海道大学大学院歯学研究院 口腔健康科学分野 硬組織発生生物学教室
  • URL: https://www.den.hokudai.ac.jp/anatomy2/hokudai_d/index.html
• [Remarks] 北海道大学大学院歯学研究院・歯学院・歯学部
  • URL: https://www.den.hokudai.ac.jp/
• [Remarks] 北海道大学大学院歯学研究院・大学院歯学院・歯学部
  • URL: https://www.den.hokudai.ac.jp/
• [Remarks] 北海道大学大学院歯学研究科 口腔健康科学講座 硬組織発生生物学教室ホームページ
  • URL: http://www.den.hokudai.ac.jp/anatomy2/hokudai_d/index.html