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Different integrins are essential to the specific responses of bone cells to variable mechanical stimuli

Research Project

Project/Area Number 25350542
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionKanagawa Dental College

Principal Investigator

Mikuni-Takagaki Yuko  神奈川歯科大学, 歯学研究科(研究院), 特任教授 (60050689)

Co-Investigator(Kenkyū-buntansha) TANAKA Takahiro  神奈川歯科大学, 歯学部, 研究員 (90550830)
Co-Investigator(Renkei-kenkyūsha) MORISHITA Shin  横浜国立大学, 研究院環境情報研究科, 教授 (80166404)
Research Collaborator HARRISON Andrew  
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords骨細胞(osteocyte) / 骨芽細胞(osteoblast) / 力学刺激 / インテグリン / 細胞分化 / 骨細胞 / 骨芽細胞 / メカニカルストレス / メカノトランスダクション / 骨細胞分化 / 伸展刺激 / 低出力超音波パルス / 顎骨壊死 / ビスフォスフォネート
Outline of Final Research Achievements

Previous studies of our own and others showed that α5β1 integrin is involved in the mechanical response of osteoblasts to low-intensity pulsed ultrasound (LIPUS) and αvβ3 integrin is involved in that of osteocytes to stretching, respectively. In this study, we further show that differentiation of osteoblasts to osteocytes was accelerated by LIPUS resulting in the increased expression of αvβ3 integrin. Treating isolated osteoblasts with neutralizing antibody to α5β1 integrin prior to the LIPUS exposure inhibited both mechanical response to LIPUS and the increased expression ofαvβ3 integrin. Prior treatment with the inhibitor of Mitogen-Activated Protein Kinase ERK1/2, PD98059, however, did not. LIPUS prevents apoptosis and induce bone remodeling also through α5β1 integrin by the increased expression of BCl-2 and RANKL in the mandibular osteoblasts, in which mechanical loading is essential for homeostasis.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (33 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Acknowledgement Compliant: 4 results,  Open Access: 8 results) Presentation (16 results) (of which Int'l Joint Research: 1 results,  Invited: 6 results) Book (5 results)

  • [Int'l Joint Research] Rutgers, New Jersey Medical School/Baylor College of Dentistry(米国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Bioventus Cooperatief(オランダ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Alendronate does not prevent long bone fragility in an inactive rat model.2016

    • Author(s)
      Naruse K, Uchida K, Suto M, Miyagawa K, Kawata A, Urabe K, Takaso M, Itoman M, Mikuni-Takagaki Y
    • Journal Title

      J Bone Miner Metab.

      Volume: 34 Issue: 6 Pages: 1-12

    • DOI

      10.1007/s00774-015-0714-y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Low-intensity pulsed ultrasound induces apoptosis in osteoclasts: Fish scales are a suitable model for the analysis of bone metabolism by ultrasound.2016

    • Author(s)
      Suzuki N, Hanmoto T, Yano S, Furusawa Y, Ikegame M, Tabuchi Y, Kondo T, Kitamura K, Endo M, Yamamoto T, Sekiguchi T, Urata M, Mikuni-Takagaki Y, Hattori A.
    • Journal Title

      Comp. Biochem. Physiol. Part A

      Volume: 195 Pages: 26-31

    • DOI

      10.1016/j.cbpa.2016.01.022

    • NAID

      120005743920

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Mode & mechanism of low intensity pulsed ultrasound (LIPUS) in fracture repair.2016

    • Author(s)
      Harrison A, Lin S, Pounder N, Mikuni-Takagaki Y
    • Journal Title

      Ultrasonics,70:.2016 doi:

      Volume: 70 Pages: 45-52

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 魚類のウロコを用いた宇宙生物学的研究:キンギョのウロコ及び骨疾患モデ ルラットの骨代謝に対するブロモメラトニンの新規作用2016

    • Author(s)
      鈴木信雄,矢野幸子,大森克徳,北村敬一郎,清水宣明,西 内 巧,染井正徳,関口俊男,渡辺良成,池亀美華,近藤 隆,田渕圭章, 鈴木 徹,遠藤雅人,竹内俊郎,江尻貞一,三島弘幸,嶋津 徹,関 あずさ,舟橋久幸,高垣裕子,笠原春夫,永瀬 睦,田谷敏貴,長野慎太郎,宮下知之,服部淳彦
    • Journal Title

      Space Utiliz Res

      Volume: 29 Pages: 87-90

    • Related Report
      2015 Annual Research Report
    • Open Access
  • [Journal Article] I-3 Effect of Low-Intensity Pulsed Ultrasound (LIPUS) in Rats With Healing Socket.2015

    • Author(s)
      Hidaka K, Miyamoto C, Takahashi SW, Saita M, Kawamata R, Maehata Y, Minabe M, Takahashi S, Mikuni-Takagaki Y.
    • Journal Title

      Journal of Orthopaedic Trauma

      Volume: 29 Issue: 5 Pages: S2-S3

    • DOI

      10.1097/01.bot.0000462954.94859.a3

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Humoral response to therapeutic low-intensity pulsed ultrasound (LIPUS) treatment of rat maxillary socket after the removal of a molar tooth2015

    • Author(s)
      Hidaka K, Miyamoto C, Wada-Takahashi S, Saita M, Kawata A, Kawamata R, Maehata Y, Minabe M, Takahashi S-S, Mikuni-Takagaki Y
    • Journal Title

      J Anal Bio-Sci

      Volume: 3 Pages: 17-24

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Dysregulated gene expression in the primary osteoblasts and osteocytes isolated from hypophosphatemic Hyp mice.2014

    • Author(s)
      Miyagawa K, Yamazaki M, Kawai M, Nishino J, Koshimizu T, Ohata Y, Tachikawa K, Mikuni-Takagaki Y, Kogo M, Ozono K, Michigami T
    • Journal Title

      PLoS One

      Volume: 9 Issue: 4 Pages: 0-0

    • DOI

      10.1371/journal.pone.0093840

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A not-so-systematic review. Comment on Low-intensity pulsed ultrasonography versus electrical stimulation for fracture healing2014

    • Author(s)
      Heeckt P, Goost H, Lin SS, McKinley TO, Mehta S, Mikuni-Takagaki Y
    • Journal Title

      Can J Surg

      Volume: 57

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Introduction: The 17th Annual Meeting of the Japanese Research Society of Ultrasound Stimulation for Fracture Repair2014

    • Author(s)
      Mikuni-Takagaki Y
    • Journal Title

      J Orthop Trauma

      Volume: 28 Issue: 6 Pages: S1-S1

    • DOI

      10.1097/bot.0000000000000118

    • Related Report
      2014 Research-status Report
    • Open Access
  • [Journal Article] Disruption of NF-κB1 prevents bone loss caused by mechanical unloading.2013

    • Author(s)
      Nakamura H, Aoki K, Masuda W, Alles N, Nagano K, Fukushima H, Osawa K, Yasuda H, Nakamura I, Mikuni-Takagaki Y, Ohya K, Maki K, Jimi E.
    • Journal Title

      J Bone Miner Res.

      Volume: 28 Issue: 6 Pages: 1457-1467

    • DOI

      10.1002/jbmr.1866

    • NAID

      10031169015

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 高齢ラット抜歯窩に照射した低出力超音波パルスが遠隔の骨髄に及ぼす影響 Effect of Low-intensity Pulsed Ultrasound on remote bone marrow in Rats with Healing Socket.2016

    • Author(s)
      日髙恒輝,宮本千央,河田亮,斉田牧子,川股亮太,前畑洋次郎,三辺正人,高橋聡子,高橋俊介,高垣裕子
    • Organizer
      第19回 超音波骨折治療研究会
    • Place of Presentation
      東京都品川区
    • Year and Date
      2016-01-23
    • Related Report
      2015 Annual Research Report
  • [Presentation] 魚類のウロコを用いた宇宙生物学的研究:宇宙実験に基づいた骨疾患の治療薬の開発.2016

    • Author(s)
      鈴木信雄,矢野幸子,関 あずさ,高垣裕子,関口俊男,染井正徳,北村敬一郎,田渕圭章,池亀美華,遠藤雅人,三島弘幸,服部淳彦
    • Organizer
      第30回宇宙環境利用シンポジウム
    • Place of Presentation
      相模原市
    • Year and Date
      2016-01-19
    • Related Report
      2015 Annual Research Report
  • [Presentation] 低出力超音波パルスの破骨細胞に対する作用.2015

    • Author(s)
      半本泰三,田渕圭章,近藤 隆,北村敬一郎,関口俊男,高垣裕子,服部淳彦,鈴木信雄
    • Organizer
      平成27年度日本動物学会大会
    • Place of Presentation
      津市
    • Year and Date
      2015-11-28
    • Related Report
      2015 Annual Research Report
  • [Presentation] 顎骨における力学的刺激伝達と低出力超音波パルスによる骨折治癒のメカニズム Oral mechanotransduction and mechanisms of fracture healing induced by Low Intensity Pulsed Ultrasound2015

    • Author(s)
      高垣裕子
    • Organizer
      第4回 Digital Orthodontics研究会大会シンポシウム
    • Place of Presentation
      福岡市
    • Year and Date
      2015-05-28
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 「骨・軟骨細胞における低出力超音波パルスによる骨折治癒のシグナル伝達」.2015

    • Author(s)
      高垣裕子
    • Organizer
      第42回日本生体電気・物理刺激研究会シンポジウム1「メカニカルストレスの生体受容機構」
    • Place of Presentation
      東京
    • Year and Date
      2015-03-14
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Low-intensity Pulsed Ultrasound Prevents Malhealing of Infected Rat Extraction Socket.2015

    • Author(s)
      Hidaka K, Miyamoto C, Kawamata R, Wada-Takahashi S, Takahashi S-S, Maehata Y, Saita M, Sato T, Taniguchi M, Kawata M, Ozaki Y, Funayama Y, Watabe H, Tani-Ishii N, Hamada N, Deguchi S, Mikuni-Takagaki Y
    • Organizer
      93rd General Session & Exhibition of the IADR/44th Annual Meeting of the AADR/39th Annual Meeting of the CADR
    • Place of Presentation
      Boston, USA
    • Year and Date
      2015-03-11 – 2015-03-14
    • Related Report
      2014 Research-status Report
  • [Presentation] ラット抜歯窩に照射した低出力超音波パルスが全身的に及ぼす影響 Effect of Low-intensity Pulsed Ultrasound in Rats with Healing Socket.2015

    • Author(s)
      日髙恒輝,宮本千央,高橋聡子,斉田牧子,川股亮太,前畑洋次郎,三辺正人,高橋俊介,高垣裕子
    • Organizer
      第18回 超音波骨折治療研究会
    • Place of Presentation
      神戸
    • Year and Date
      2015-01-17
    • Related Report
      2014 Research-status Report
  • [Presentation] ラット抜歯窩に照射した低出力超音波パルス (LIPUS) が全身に及ぼす影響2014

    • Author(s)
      日髙恒輝, 宮本千央, 高橋聡子, 斉田牧子, 川股亮太, 前畑洋次郎, 三辺正人, 高橋俊介, 高垣裕子
    • Organizer
      第49回神奈川歯科大学学会総会
    • Place of Presentation
      横須賀
    • Year and Date
      2014-11-29
    • Related Report
      2014 Research-status Report
  • [Presentation] 抜歯窩に照射した低出力超音波パルスがラットに与える影響 Effect of Low-intensity Pulsed Ultrasound in Rats with Healing Socket.2014

    • Author(s)
      日髙恒輝, 高橋俊介, 高橋聡子, 根本賢治, 岩崎和人, 秋月達也, 高垣裕子, 三辺正人: 抜歯窩に照射した低出力超音波パルスがラットに与える影響 Effect of Low-intensity Pulsed Ultrasound in Rats with Healing Socket.
    • Organizer
      第57回秋季日本歯周病学会学術大会
    • Place of Presentation
      神戸
    • Year and Date
      2014-10-19 – 2014-10-20
    • Related Report
      2014 Research-status Report
  • [Presentation] 教育講演 ナノインデンテ^ション法(非侵襲的な骨の強度計測法)2014

    • Author(s)
      高垣裕子
    • Organizer
      2014年 骨形態フォーラム
    • Place of Presentation
      大分
    • Year and Date
      2014-09-20 – 2014-09-21
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Effect of Therapeutic Low-intensity Pulsed Ultrasound (LIPUS) after the Treatment of Rat Extraction Socket.2014

    • Author(s)
      Hidaka K, Miyamoto C, Wada-Takahashi S, Kawamata R, Maehata Y, Minabe M, Takahasi S-S, Mikuni-Takagaki Y
    • Organizer
      FEBS EMBO 2014 Conference
    • Place of Presentation
      Paris, France
    • Year and Date
      2014-08-30 – 2014-09-04
    • Related Report
      2014 Research-status Report
  • [Presentation] 骨再生における超音波によるシグナル伝達.2014

    • Author(s)
      高垣裕子
    • Organizer
      日本超音波医学会第87回学術集会シンポジウム「分子基盤に立った超音波の治療応用」
    • Place of Presentation
      東京
    • Year and Date
      2014-05-09
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] LIPUS (Low-intensity Pulsed Ultrasound) Prevents BRONJ-like Pathology in an Ovariectomized Rat Model2014

    • Author(s)
      Hidaka K. et al.
    • Organizer
      International Bone & Mineral Society: 2014 Herbert Fleisch Workshop
    • Place of Presentation
      Brugge,Belgium
    • Related Report
      2013 Research-status Report
  • [Presentation] メカニカルストレスに対して部位特異的な骨の応答

    • Author(s)
      高垣裕子
    • Organizer
      第33回日本骨形態計測学会シンポジウム
    • Place of Presentation
      浜松
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] 骨再生における超音波によるシグナル伝達

    • Author(s)
      高垣裕子
    • Organizer
      日本超音波医学会第87回学術集会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
    • Invited
  • [Presentation] ラット顎骨壊死モデルの作製と低出力超音波パルス照射による病態の改善

    • Author(s)
      日髙恒輝他
    • Organizer
      第13回 日本再生医療学会総会
    • Place of Presentation
      京都
    • Related Report
      2013 Research-status Report
  • [Book] 加速矯正―基礎と臨床―: 2-1骨折治癒のメカニズム・4-1低出力超音波刺激による骨折・創傷治癒促進のメカニズム・Q & A2016

    • Author(s)
      高垣裕子(久保田隆朗・Rohit C. L. Sachdeva編)
    • Total Pages
      122
    • Publisher
      東京臨床出版
    • Related Report
      2015 Annual Research Report
  • [Book] メカノバイオロジー―細胞が力を感じ応答する仕組み: 15章口腔におけるメカノバイオロジー2016

    • Author(s)
      高垣裕子 (曽我部正博編)
    • Publisher
      化学同人
    • Related Report
      2015 Annual Research Report
  • [Book] メカノバイオロジー(15章口腔におけるメカノバイオロジー)2015

    • Author(s)
      高垣裕子(分担)
    • Total Pages
      10
    • Publisher
      化学同人
    • Related Report
      2014 Research-status Report
  • [Book] 生体電気・物理刺激による 骨・軟部組織修復法 (低出力超音波刺激に対する細胞応答)2013

    • Author(s)
      高垣裕子(分担)
    • Total Pages
      304
    • Publisher
      金芳堂
    • Related Report
      2013 Research-status Report
  • [Book] 新しい骨形態計測 (ナノインデンテーション法)2013

    • Author(s)
      高垣裕子・田中隆博(分担)
    • Total Pages
      232
    • Publisher
      ウイネット
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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