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Bone-specific action of parathyroid hormone on membrane transporters and enzymes involved in phosphate ion supplement

Research Project

Project/Area Number 18H02964
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 57010:Oral biological science-related
Research InstitutionHokkaido University

Principal Investigator

AMIZUKA Norio  北海道大学, 歯学研究院, 教授 (30242431)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2020: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2019: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2018: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Keywords石灰化 / リン酸供与膜輸送体 / 副甲状腺ホルモン / 骨芽細胞 / 微細構造
Outline of Final Research Achievements

The purpose of this study is to evaluate if the synthesis and supply of phosphate ions -a constituent of calcified bone matrix- is regulated by serum concentration of parathyroid hormone (PTH). PTH-administered mice showed the increased expression of TNAP, ENPP1, ANK, PHOSPHO1 and SIBLING family, consequently resulting in highly-calcified bone matrix. In contrast, NaPiIIa/IIc mice bearing hypophosphatemia revealed no change of TNAP, ENPP1, ANK, PHOSPHO1 genes and SIBLING family, showing less amount of bone volume. Hyp mice - another hypophosphatemia model due to mutation in Phex-demonstrated huge areas of uncalcified bone matrix. Taken together, it seems likely that PTH increases the synthesis and supply of phosphate ions in bone, while calcification in bone matrix is regulated by Phex/SIBLING family.

Academic Significance and Societal Importance of the Research Achievements

超高齢化社会を迎えた現在、骨をはじめとする運動器の健康維持はヒトの健康寿命を延ばすうえで大きく貢献すると思われる。特に、骨強度に深く関与する骨基質石灰化は、血清カルシウム(Ca)とリンによって規定されると考えられているが、血清Ca濃度はほぼ一定に維持されていることから、血清リン濃度変化による骨基質石灰化が注目を浴びている。特に、骨基質石灰化において、骨代謝に影響を与える副甲状腺ホルモンによるリン酸供与作用の検索は、基礎研究から骨基質石灰化のメカニズムを解明することに繋がり、正常あるいは病的石灰化において重要な情報を与えると考えられる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (40 results)

All 2021 2020 2019 2018 Other

All Journal Article (14 results) (of which Int'l Joint Research: 6 results,  Peer Reviewed: 14 results,  Open Access: 7 results) Presentation (21 results) (of which Int'l Joint Research: 7 results,  Invited: 8 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Frequent administration of abaloparatide shows greater gains in bone anabolic window and bone mineral density in mice: A comparison with teriparatide.2021

    • Author(s)
      Makino A., Hasegawa T., Takagi H., Takahashi Y., Hase N., Amizuka N.
    • Journal Title

      Bone.

      Volume: 142巻 Pages: 115651-115651

    • DOI

      10.1016/j.bone.2020.115651

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Altered immunolocalization of FGF23 in murine femora metastasized with human breast carcinoma MDA-MB-231 cells.2021

    • Author(s)
      Yokoyama A., Hasegawa T., Hiraga T., Yamada T., Yimin, Hongo H., Yamamoto T., Abe M., Yoshida T., Imanishi Y., Kuroshima S., Sasaki M., Freitas PHL., Li M., Amizuka N., Yamazaki Y.
    • Journal Title

      J Bone Miner Metab.

      Volume: 印刷中 Issue: 5 Pages: 810-823

    • DOI

      10.1007/s00774-021-01220-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass2020

    • Author(s)
      Moriishi Takeshi、Ozasa Ryosuke、Ishimoto Takuya、Nakano Takayoshi、Hasegawa Tomoka、Miyazaki Toshihiro、Liu Wenguang、Fukuyama Ryo、Wang Yuying、Komori Hisato、Qin Xin、Amizuka Norio、Komori Toshihisa
    • Journal Title

      PLOS Genetics

      Volume: 16 Issue: 5 Pages: 1008586-1008586

    • DOI

      10.1371/journal.pgen.1008586

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Osteocytic Osteolysis in PTH-treated Wild-type and Rankl-/- Mice Examined by Transmission Electron Microscopy, Atomic Force Microscopy, and Isotope Microscopy.2020

    • Author(s)
      Hongo H., Hasegawa T., Saito M., Tsuboi K., Yamamoto T., Sasaki M., Abe M., Freitas PHL., Yurimoto H., Udagawa N., Li M., Amizuka N.
    • Journal Title

      J Histochem Cytochem.

      Volume: 68 Issue: 10 Pages: 651-668

    • DOI

      10.1369/0022155420961375

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Immunocytochemical assessment of cell differentiation of podoplanin-positive osteoblasts into osteocytes in murine bone.2020

    • Author(s)
      Nagai T., Hasegawa T., Yimin, Yamamoto T., Hongo H., Abe M., Yoshida T., Yokoyama A., Freitas PHL., Li M., Yokoyama A., Amizuka N.
    • Journal Title

      Histochem Cell Biol.

      Volume: 155 Issue: 3 Pages: 369-380

    • DOI

      10.1007/s00418-020-01937-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Intermittent PTH administration increases bone specific-blood vessels and surrounding stromal cells in murine long bones.2020

    • Author(s)
      Zhao S., Hasegawa T., Hongo H., Yamamoto T., Abe M., Yoshida T., Haraguchi M., Freitas PHL., Li M., Tei K., Amizuka N.
    • Journal Title

      Calcif Tissue Int.

      Volume: 108 Issue: 3 Pages: 391-406

    • DOI

      10.1007/s00223-020-00776-2

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of sodium-dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages.2020

    • Author(s)
      Hanazaki A, Ikuta K, Sasaki S, Sasaki S, Koike M, Tanifuji K, Arima Y, Kaneko I, Shiozaki Y, Tatsumi S, Hasegawa T, Amizuka N, Miyamoto KI, Segawa H.
    • Journal Title

      Physiol Rep.

      Volume: Feb;8(3) Issue: 3 Pages: 1-16

    • DOI

      10.14814/phy2.14324

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass.2020

    • Author(s)
      Moriishi T., Ozasa R., Ishimoto T., Liu W., Hasegawa T., Amizuka N., Komori T.
    • Journal Title

      PLOS Genetics.

      Volume: in press

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-dimensional morphology of the Golgi apparatus in osteoclasts: NADPase and arylsulfatase cytochemistry, and scanning electron microscopy using osmium maceration.2019

    • Author(s)
      Yamamoto T., Hasegawa H., Hongo H., Amizuka N.
    • Journal Title

      Microscopy

      Volume: 68巻3号 Issue: 3 Pages: 243-253

    • DOI

      10.1093/jmicro/dfz003

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] 副甲状腺ホルモン製剤の骨形成作用について2019

    • Author(s)
      長谷川智香、宮本幸奈、山本知真也、網塚憲生
    • Journal Title

      日本薬理学会雑誌

      Volume: 153 Pages: 16-21

    • NAID

      130007556041

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Eldecalcitol Causes FGF23 Resistance for Pi Reabsorption and Improves Rachitic Bone Phenotypes in the Male Hyp Mouse.2018

    • Author(s)
      Kaneko I, Segawa H, Ikuta K, Hanazaki A, Fujii T, Tatsumi S, Kido S, Hasegawa T, Amizuka N, Saito H, Miyamoto KI.
    • Journal Title

      Endocrinology

      Volume: 159(7) Issue: 7 Pages: 2741-2758

    • DOI

      10.1210/en.2018-00109

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Histological Effects of the Combined Administration of Eldecalcitol and a Parathyroid Hormone in the Metaphyseal Trabeculae of Ovariectomized Rats2018

    • Author(s)
      Hasegawa T., Yamamoto T., Sakai S., Miyamoto Y., Hongo H., Qiu Z., Abe M., Takeda S., Oda K., Freitas PHL., Li M., Endo K., Amizuka N.
    • Journal Title

      Journal of Histochemistry & Cytochemistry

      Volume: 67 Issue: 3 Pages: 169-184

    • DOI

      10.1369/0022155418806865

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sequential Treatment with Eldecalcitol After PTH Improves Bone Mechanical Properties of Lumbar Spine and Femur in Aged Ovariectomized Rats2018

    • Author(s)
      Sakai S., Hongo H., Yamamoto T., Hasegawa T., Takeda S., Saito H., Endo K., Yogo Y., Amizuka N.
    • Journal Title

      Calcified Tissue International

      Volume: 104 Issue: 3 Pages: 251-261

    • DOI

      10.1007/s00223-018-0497-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] FGF23/klothoシグナルによる基質石灰化制御機構の解明2018

    • Author(s)
      長谷川智香、宮本幸奈、邱 紫セン、阿部未来、本郷裕美、網塚憲生
    • Journal Title

      日本骨粗鬆症学会雑誌

      Volume: 4 Pages: 134-136

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Presentation] PTH間歇投与マウス大腿骨におけるpodoplanin/PHOSPHO1陽性骨芽細胞の局在2021

    • Author(s)
      中島悠斐、山本知真也、本郷裕美、網塚憲生、長谷川智香
    • Organizer
      第126回日本解剖学会総会・全国学術集会/第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Remodeling/Modeling-based bone formationの組織学2020

    • Author(s)
      網塚憲生、長谷川智香、本郷裕美、山本知真也
    • Organizer
      第40回日本骨形態計測学会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 動物モデルを用いた骨組織再生の顕微学的検索2020

    • Author(s)
      網塚憲生、長谷川智香
    • Organizer
      公益社団法人日本セラミックス協会第33回秋季シンポジウム
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 骨血管連関からみた骨芽細胞系細胞の分化2020

    • Author(s)
      長谷川智香、趙 申、吉野弘菜、阿部未来
    • Organizer
      第62回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Abaloparatide promotes bone repair of vertebral defects in an overiectomized rat model of osteoporosis2020

    • Author(s)
      Makino A., Hasegawa T., Takagi H., Takahashi Y., Hase N., Amizuka N.
    • Organizer
      World Congress on Osteoporosis, Osteoarthritis and Musculoskeletal Diseases 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Abaloparatide promotes bone repair of vertebral defects in an overiectomized rat model of osteoporosis2020

    • Author(s)
      Makino A., Hasegawa T., Takagi H., Takahashi Y., Hase N., Amizuka N.
    • Organizer
      The American Society for Bone and Mineral Research 2020 Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 副甲状腺ホルモン間歇投与による皮質骨多孔化の組織化学的検索2020

    • Author(s)
      阿部未来、山本知真也、本郷裕美、網塚憲生、長谷川智香
    • Organizer
      第62 回歯科基礎医学会学術大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] モデリングおよび骨リモデリング領域の骨芽細胞の活性化における組織細胞学的検索2020

    • Author(s)
      阿部未来、長谷川智香、宇田川信之、網塚憲生
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] PTH投与による高骨代謝回転状態でのpodoplanin/PHOSPHO1陽性骨芽細胞の局在2020

    • Author(s)
      中嶋悠斐、山本知真也、本郷裕美、網塚憲生、長谷川智香
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 椎体を欠損させた卵巣摘除ラットにおけるアバロパラチドの骨欠損修復促進作用2020

    • Author(s)
      槙野彰人、長谷川智香、網塚憲生
    • Organizer
      第38回日本骨代謝学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 歯科領域の骨再生における細胞学的・微細構造学的検索 -動物モデルの顕微解析2020

    • Author(s)
      網塚憲生、本郷裕美、長谷川智香
    • Organizer
      第19回日本再生医療学会総会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] 骨血管連関における細胞間コミュニケーション2020

    • Author(s)
      長谷川智香、本郷裕美、山本知真也、網塚憲生
    • Organizer
      第125回日本解剖学会総会・全国学術集会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Histochemical assessment for bone/vascular mineralization of kl/kl and αklotho-/- mice.2019

    • Author(s)
      Hasegawa T.: Yamamoto T., Miyamoto Y., Qiu Z., Hongo H., Amizuka N.
    • Organizer
      The 7th Seoul Symposium on Bone Health & the 31th Spring Scientific Congress of the Korean Society for Bone and Mineral Research
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cellular mechanism of abnormal mineralization of bone and aorta induced by the disrupted function of FGF23/klotho.2019

    • Author(s)
      Hasegawa T., Miyamoto-Takasaki Y., Qiu Z., Yamamoto T., Amizuka N.
    • Organizer
      97thGeneral Session & Exhibition of The International Association for Dental Research (IADR), 48th Annual Meeting of The AADR, 43rd Annual Meeting of THE CADR
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Histochemical assessment of abnormal mineralization in bone and aorta induced by disrupted FGF23/αklotho.2019

    • Author(s)
      Hasegawa T., Yamamoto T., Miyamoto Y., Qiu Z., Hongo H., Amizuka N.
    • Organizer
      The American Society for Bone and Mineral Research (ASBMR) 2019Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The biological effect of bone-specific blood vessels by intermittent PTH administration in mice.2019

    • Author(s)
      Zhao S., Hasegawa T., Tei K., Amizuka N.
    • Organizer
      日本解剖学会第 65 回東北・北海道連合支部学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 骨粗鬆症モデルラットにおけるエルデカルシトール誘導性ミニモデリングの組織化学的解析2019

    • Author(s)
      長谷川智香、山本知真也、本郷裕美、武田 聡、坂井貞興、與語健二、松本義弘、網塚憲生
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Jansen 型PTH/PTHrP受容体変異トランスジェニックマウスの形態および機能異常解析2019

    • Author(s)
      下村-黒木淳子、梨田智子、森田貴雄、大島勇人、網塚憲生
    • Organizer
      第61回歯科基礎医学会学術大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Abnormal Mineralization in Bone and Aorta Induced by the Disrupted Function of FGF23/klotho.2019

    • Author(s)
      Hasegawa T., Miyamoto Y., Qiu Z., Yamamoto T., Amizuka N.
    • Organizer
      International Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Histological Assessment of Bone Formation Induced by the New Bone Prosthetic Material Contained Phosphorylated-Pullulan.2019

    • Author(s)
      Hasegawa T., Hongo H., Qiu Z., Miyamoto Y., Amizuka N.
    • Organizer
      International Collaborative Symposium on Development of Human Resources in Practical Oral Health and Treatment
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 骨基質石灰化におけるリン-FGF23-Klotho axis2018

    • Author(s)
      網塚憲生、長谷川智香、邱 紫セン、本郷裕美
    • Organizer
      第63回日本透析医学会学術集会・総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Book] 副甲状腺・骨代謝疾患診療マニュアル改訂第2版2019

    • Author(s)
      長谷川智香、宮本幸奈、網塚憲生
    • Total Pages
      264
    • Publisher
      診断と治療社
    • ISBN
      9784787823748
    • Related Report
      2019 Annual Research Report
  • [Book] 副甲状腺・骨代謝疾患診療マニュアル2019

    • Author(s)
      長谷川智香、宮本幸奈、網塚憲生
    • Publisher
      診断と治療社
    • Related Report
      2018 Annual Research Report
  • [Book] CKD-MBD 3rd Edition2018

    • Author(s)
      網塚憲生、邱 紫セン、長谷川智香
    • Total Pages
      320
    • Publisher
      日本メディカルセンター
    • ISBN
      9784888753081
    • Related Report
      2018 Annual Research Report
  • [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/

    • Related Report
      2018 Annual Research Report
  • [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

    • Related Report
      2018 Annual Research Report

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Published: 2018-04-23   Modified: 2022-01-27  

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