Novel biological actions of PTH mediated by osteocyte network - mini-modeling and osteocytic osteolysis

• Project/Area Number: 26670797
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Morphological basic dentistry
• Research Institution: Hokkaido University
• Principal Investigator: AMIZUKA Norio 北海道大学, 歯学研究科(研究院), 教授 (30242431)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: PTH / 骨形成 / 骨細胞 / 骨細胞性骨溶解 / ミニモデリング / 骨リモデリング / リモデリング / 骨芽細胞 / 前骨芽細胞 / 電子顕微鏡

Outline of Final Research Achievements

We have attempted to clarify the bipartite biological action of parathyroid hormone (PTH) on bone metabolism, -anabolic effects and osteocytic osteolysis. We have examined PTH-driven anabolic effects in mice at the regimens of high and low frequent administration. As a consequence, the high frequent PTH administration formed many trabeculae, whereas the low frequent administration induced thick trabeculae; the former seemed to be caused by accelerated bone remodeling, while the latter is resulted from both bone remodeling and mini-modeling (a manner of bone formation independent of osteoclastic bone resorption). Unlike the anabolic effect of PTH, enlarged osteocytic lacunae were observed after several hours of PTH administration - osteocytic osteolysis -, and then, calcium phosphates were deposited on walls of the once-enlarged lacunae.

Research Products

• [Journal Article] Immunolocalization of osteocyte-derived molecules during bone fracture healing of mouse ribs. (2016)
  • Author(s): Liu Z., Yamamoto T., Hasegawa T., Hongo H., Tsuboi K., Tsuchiya E., Haraguchi M., Abe M., Freitas PHL., Kudo A., Oda K., Li M., Amizuka N.
  • Journal Title: Biomedical Research Volume: 37 Pages: 141-151
  • NAID: 130005147430
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Treatment with eldecalcitol positively affects mineralization, microdamage, and collagen crosslinks in primate bone. (2015)
  • Author(s): Saito M, Grynpas MD, Burr DB, Allen MR, Smith SY, Doyle N, Amizuka N, Hasegawa T, Kida Y, Marumo K, Saito H.
  • Journal Title: Bone. Volume: 73 Pages: 8-15
  • DOI: 10.1016/j.bone.2014.11.025
  • Peer Reviewed / Open Access
• [Journal Article] Osteoblast-Specific γ-Glutamyl Carboxylase-Deficient Mice Display Enhanced Bone Formation with Aberrant Mineralization. (2015)
  • Author(s): Azuma K, Shiba S, Hasegawa T, Ikeda K, Urano T, Horie-Inoue K, Ouchi Y, Amizuka N, Inoue S
  • Journal Title: J Bone Miner Res. Volume: 未定 Issue: 7 Pages: 1245-1254
  • DOI: 10.1002/jbmr.2463
  • Peer Reviewed / Open Access
• [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: Histol Histopathol. Volume: 30 Pages: 77-85
  • Peer Reviewed
• [Journal Article] Altered distribution of extracellular matrix proteins in the periodontal ligament of periostin-deficient mice. (2014)
  • Author(s): Tabata C., Hongo H., Sasaki M., Hasegawa T., de Freitas PH., Yamada T., Yamamoto T., Suzuki R., Yamamoto T., Oda K., Li M., Kudo A., Iida J., Amizuka N.
  • Journal Title: Histol Histopathol. Volume: 29 Pages: 731-742
  • Peer Reviewed
• [Presentation] Histochemical examination on bone matrix surrounding osteocytic lacunae in mice with PTH administration and in lactating mice fed with calcium insufficient diet. (2015)
  • Author(s): Hongo H., Sasaki M., Saito M., Udagawa N., Amizuka N.
  • Organizer: Australian and New Zealand Bone and Mineral Society (ANZBMS) 2015 Joint ANZBMS, MEPSA and MBSANZ Annual Scientific Meeting
  • Place of Presentation: ホバート(オーストラリア)
  • Year and Date: 2015-11-01
  • Int'l Joint Research
• [Presentation] Histochemical examination on bone of postmenopausal model rats with switched administration from PTH to eldecalcitol. (2015)
  • Author(s): Hongo H., Sasaki M., Saito M., Udagawa N., Amizuka N.
  • Organizer: The American Society for Bone and Mineral Research (ASBMR) 2015Annual Meeting
  • Place of Presentation: シアトル(アメリカ合衆国)
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] オーバービュー：骨を観る －組織化学・微細構造学からバイオイメージングへの展開－． (2015)
  • Author(s): 網塚憲生、長谷川智香、坪井香奈子、本郷裕美、原口真衣、山本知真也
  • Organizer: 第57回歯科基礎医学会学術大会
  • 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: 2015-09-11
  • Invited
• [Presentation] PTHの投与頻度の違いによるリモデリング・ミニモデリングを基盤とした骨形成． (2015)
  • Author(s): 山本知真也、長谷川智香、本郷裕美、原口真衣、織田公光、網塚憲生
  • Organizer: 第57回歯科基礎医学会学術大会
  • 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: 2015-09-11
• [Presentation] 細胞組織学からみた骨粗鬆症治療薬の作用機序． (2015)
  • Author(s): 網塚憲生、山本知真也、本郷裕美、長谷川智香
  • Organizer: 第35回日本骨形態計測学会
  • Place of Presentation: 倉敷市芸文館(岡山県倉敷市)
  • Year and Date: 2015-06-04
  • 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
• [Presentation] 副甲状腺ホルモン投与後、または、カルシウム欠乏食で飼育されたマウスの授乳期における骨小腔周囲の骨基質の組織学的検索． (2015)
  • Author(s): 本郷裕美、佐々木宗輝、齋藤雅美、宇田川信之、網塚憲生
  • Organizer: 第120回日本解剖学会総会・全国学術集会第92回日本生理学会大会合同大会
  • Place of Presentation: 神戸国際会議場・展示場（兵庫県・神戸市）
  • Year and Date: 2015-03-21 – 2015-03-23
• [Presentation] Eldecalcitol, a new-generation vitamin D3 analog, increases trabecular bone via “minimodeling” in ovariectomized cynomolgus monkeys. (2014)
  • Author(s): Hasegawa T., Saito M., Doyle N., Chouinard L., Smith SY., Yamamoto T., Oda K., Saito H., Amizuka N.
  • Organizer: The American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting
  • Place of Presentation: ヒューストン（アメリカ合衆国）
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] Effects of the Combination of Eldecalcitol, an Analog of Active Vitamin D3, and Parathyroid Hormone in Ovariectomized Rat Bones. (2014)
  • Author(s): Yamamoto T., Hasegawa T., Sakai S., Takeda S., Oda K., Li M., Endo K., Amizuka N.
  • Organizer: The American Society for Bone and Mineral Research (ASBMR) 2014 Annual Meeting
  • Place of Presentation: ヒューストン（アメリカ合衆国）
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] 骨細胞・ 骨細管系における形態学的アプローチ． (2014)
  • Author(s): 網塚憲生、本郷裕美、坪井香奈子、山本知真也、長谷川智香
  • 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（大阪府・大阪市）
  • Year and Date: 2014-07-24 – 2014-07-26
  • Invited
• [Presentation] 副甲状腺ホルモン製剤に対する骨の細胞群の反応 －組織学的知見－． (2014)
  • Author(s): 網塚憲生
  • 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（大阪府・大阪市）
  • Year and Date: 2014-07-24 – 2014-07-26
  • Invited
• [Presentation] 骨粗鬆症モデルラットを用いた副甲状腺ホルモン(PTH)とエルデカルシトール併用投与の効果． (2014)
  • Author(s): 山本知真也、田中祐介、長谷川智香、坂井貞興、武田 聡、本郷裕美、佐々木宗輝、遠藤弘一、網塚憲生
  • Organizer: 第34回日本骨形態計測学会
  • Place of Presentation: さっぽろ芸文館（北海道・札幌市)
  • Year and Date: 2014-06-12 – 2014-06-14
• [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] 羊土社 (2015)
  • Author(s): 網塚憲生、長谷川智香
  • Publisher: イラストで徹底理解する 骨疾患キーワード辞典
• [Book] 女性のライフサイクルと骨 (2015)
  • Author(s): 網塚憲生、長谷川智香、原口真衣、山本知真也、本郷裕美
  • Publisher: 医薬ジャーナル社
• [Book] 「ビタミンDと疾患 改訂版 -基礎の理解と臨床への応用-」 (2014)
  • Author(s): 網塚憲生、長谷川智香、山本知真也、佐々木宗輝、本郷裕美
  • Total Pages: 248
  • Publisher: 医薬ジャーナル社
• [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
• [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
  • URL: http://www.den.hokudai.ac.jp/anatomy2/hokudai_d/index.html