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Animal study for evaluating the effect of meclozine on FGFR3 signaling

Research Project

Project/Area Number 15K10439
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionNagoya University

Principal Investigator

Matsushita Masaki  名古屋大学, 医学部附属病院, 病院助教 (60721115)

Co-Investigator(Kenkyū-buntansha) 鬼頭 浩史  名古屋大学, 医学系研究科, 准教授 (40291174)
三島 健一  名古屋大学, 医学系研究科, 寄附講座助教 (40646519)
杉浦 洋  名古屋大学, 医学部附属病院, 医員 (40750477)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
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: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords軟骨無形成症 / FGFR3 / 低身長 / メクロジン / 骨密度 / 骨質 / 大後頭孔 / 大後頭孔狭窄
Outline of Final Research Achievements

Achondroplasia (ACH) is characterized by short stature associated with severe complications such as stenoses of foramen magnum and spinal canal due to the gain-of-function mutation in fibroblast growth factor receptor 3 (FGFR3). We have already found that meclozine, an anti-histamine drug that has long been used for motion sickness, inhibited FGFR3 signaling. In the current study, the 1 or 2 mg/kg/day of meclozine increased the bone length of 7-day-old Ach mice for 10 days, but did not rescue the foramen magnum stenosis. Meclozine administration would be commenced immediately after birth since the synchondroses around the foramen magnum was closed at the age of 4.5 days. On the other hand, the 1 or 2 mg/kg/day of meclozine increased the bone volume and bone mineral density in addition to the bone length in growing Ach mice.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 4 results) Presentation (21 results) (of which Int'l Joint Research: 10 results,  Invited: 2 results)

  • [Journal Article] Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia.2018

    • Author(s)
      6.Okura T, Matsushita M, Mishima K, Esaki R, Seki T, Ishiguro N, Kitoh H.
    • Journal Title

      J Orthop Res

      Volume: 36(1) Issue: 1 Pages: 300-308

    • DOI

      10.1002/jor.23608

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical dosage of meclozine promotes longitudinal bone growth, bone volume, and trabecular bone quality in transgenic mice with achondroplasia.2017

    • Author(s)
      Matsushita M, Esaki R, Mishima K, Ishiguro N, Ohno K, Kitoh H.
    • Journal Title

      Sci Rep.

      Volume: 7 Issue: 1 Pages: 7371-7371

    • DOI

      10.1038/s41598-017-07044-8

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Activated FGFR3 promotes bone formation via accelerating endochondral ossification in mouse model of distraction osteogenesis2017

    • Author(s)
      Osawa Yusuke、Matsushita Masaki、Hasegawa Sachi、Esaki Ryusaku、Fujio Masahito、Ohkawara Bisei、Ishiguro Naoki、Ohno Kinji、Kitoh Hiroshi
    • Journal Title

      Bone

      Volume: 105 Pages: 42-49

    • DOI

      10.1016/j.bone.2017.05.016

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Maternal administration of meclozine for the treatment of foramen magnum stenosis in transgenic mice with achondroplasia2017

    • Author(s)
      Matsushita M, Mishima K, Esaki R, Ishiguro N, Ohno K, Kitoh H
    • Journal Title

      J Neurosurg Pediatr

      Volume: 19 Issue: 1 Pages: 91-95

    • DOI

      10.3171/2016.7.peds16199

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Low bone mineral density in achondroplasia and hypochondroplasia2015

    • Author(s)
      Matsushita M, Kitoh H, Mishima K, Kadono I, Sugiura H, Hasegawa S, Nishida Y, Ishiguro N
    • Journal Title

      Pediatr Int.

      Volume: 印刷中 Issue: 8 Pages: 705-708

    • DOI

      10.1111/ped.12890

    • Related Report
      2016 Research-status Report 2015 Research-status Report
    • Peer Reviewed
  • [Presentation] Bone formation was promoted in mouse model of distraction osteogenesis with gain-of-function mutation in FGFR32018

    • Author(s)
      Masaki Matsushita, Yusuke Ohsawa, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh
    • Organizer
      Fibroblast Growth Factors in Development and Disease Gordon Research Conference
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinically feasible dose of meclozine promotes bone growth in mouse model with achondroplasia2017

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Sachi Hasegawa, Akiko Kitamura, Naoki Ishiguro, Kinji Ohno
    • Organizer
      Annual Meeting - Orthopaedic Research Society (ORS)
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2017-03-19
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 軟骨無形成症の根本的治療を目指したmeclozineの有効投与量の検討2017

    • Author(s)
      松下 雅樹、 鬼頭 浩史、 三島 健一、杉浦 洋、北村 暁子、西田 佳弘、石黒 直樹、 大野 欽司
    • Organizer
      第30回日本軟骨代謝学会
    • Place of Presentation
      京都市勧業館みやこめっせ(京都府京都市)
    • Year and Date
      2017-03-03
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinically Feasible Dose of Meclozine Improves Bone Growth, Bone Volume, and Bone Quality in Mouse Model with Achondroplasia2017

    • Author(s)
      Masaki Matsushita, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno, Hiroshi Kitoh
    • Organizer
      The 27th Korean-Japanese Combined Orthopaedic Symposium 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Clinical feasibility of meclozine for improvement of short stature in achondroplasia2017

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Akiko Kitamura, Naoki Ishiguro
    • Organizer
      2017 Combined European Pediatric Orthopaedic Society/Pediatric Orthopaedic Society of North America (EPOSNA) Annual Meeting
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Meclozine投与による軟骨無形成症モデルマウスにおける骨伸張と骨質の検討2017

    • Author(s)
      松下 雅樹、 鬼頭 浩史、 三島 健一、北村 暁子、長田 侃、西田 佳弘、石黒 直樹、 大野 欽司
    • Organizer
      第32回日本整形外科学会基礎学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Meclozine投与による軟骨無形成症モデルマウスにおける骨伸張と骨質の検討2017

    • Author(s)
      松下 雅樹、 鬼頭 浩史、 三島 健一、北村 暁子、長田 侃、西田 佳弘、石黒 直樹、 大野 欽司
    • Organizer
      第35回日本骨代謝学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Activated FGFR3 prevents subchondral bone sclerosis during the development of osteoarthritis in transgenic mice with achondroplasia2017

    • Author(s)
      Toshiaki Okura, Masaki Matsushita, Kenichi Mishima, Ryusaku Esaki, Taisuke Seki, Naoki Ishiguro, Hiroshi Kitoh
    • Organizer
      Annual meeting of the American Society for Bone and Mineral Research
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 軟骨無形成症に対する根本的治療の開発2016

    • Author(s)
      松下 雅樹、 鬼頭 浩史、 三島 健一、杉浦 洋、長谷川 幸、北村 暁子、石黒 直樹、 大野 欽司
    • Organizer
      第27回日本小児整形外科学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-12-01
    • Related Report
      2016 Research-status Report
  • [Presentation] meclozineは乗り物酔い止め薬としての効能を発揮する用量の連日投与により軟骨無形成症における骨伸張を促進しうる2016

    • Author(s)
      松下 雅樹、 鬼頭 浩史、 三島 健一、杉浦 洋、西田 佳弘、石黒 直樹、 大野 欽司
    • 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
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinical feasibility of oral administration of meclozine for the treatment of short stature in achondroplasia2016

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno
    • Organizer
      American Society for Bone and Mineral Research (ASBMR) Annual Meeting
    • Place of Presentation
      Atlanta(USA)
    • Year and Date
      2016-09-15
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinically attainable concentration of meclozine has a potent effect on promoting bone growth in achondroplasia2016

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno
    • Organizer
      Annual Meetings of the Endocrine Society of Australia and Society for Reproductive Biology and Australia and New Zealand Bone and Mineral Society
    • Place of Presentation
      Gold Coast (Australia)
    • Year and Date
      2016-08-21
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] meclozineによる軟骨無形成症の根本的治療の可能性と限界2016

    • Author(s)
      松下 雅樹、 鬼頭 浩史、 三島 健一、杉浦 洋、西田 佳弘、石黒 直樹、 大野 欽司
    • Organizer
      第34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
      2016-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] Clinically attainable concentration of meclozine promotes bone growth in transgenic mice with achondroplasia2016

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno
    • Organizer
      Fibroblast Growth Factors in Development & Disease - Gordon Research Conference
    • Place of Presentation
      Hong Kong (China)
    • Year and Date
      2016-06-05
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] Radical therapeutic strategy for foramen magnum stenosis and spinal canal stenosis in achondroplasia2016

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Sachi Hasegawa, Akiko Kitamura, Naoki Ishiguro, Kinji Ohno
    • Organizer
      Orthopaedic Research Society (ORS) Annual meeting
    • Place of Presentation
      Orlando,U.S.A.
    • Year and Date
      2016-03-05
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] MeclozineはFGFR3シグナルを抑制し軟骨無形成症における低身長を改善しうる2016

    • Author(s)
      松下 雅樹、鬼頭 浩史、三島 健一、西田 佳弘、石黒 直樹、大野 欽司
    • Organizer
      第29回日本軟骨代謝学会
    • Place of Presentation
      広島大学広仁会館(広島県広島市)
    • Year and Date
      2016-02-19
    • Related Report
      2015 Research-status Report
  • [Presentation] 軟骨無形成症治療の現在と未来2016

    • Author(s)
      松下 雅樹
    • Organizer
      つくしんぼ総会
    • Place of Presentation
      大阪市長居障がい者スポーツセンター(大阪府大阪市)
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 軟骨無形成症における根本的治療薬の開発2015

    • Author(s)
      松下 雅樹、鬼頭 浩史、三島 健一、杉浦 洋、長谷川 幸、北村 暁子、西田 佳弘、石黒 直樹、大野 欽司
    • Organizer
      第27回日本整形外科学会骨系統疾患研究会
    • Place of Presentation
      長良川国際会議場(岐阜県岐阜市)
    • Year and Date
      2015-12-05
    • Related Report
      2015 Research-status Report
  • [Presentation] 軟骨無形成症治療の現在と未来2015

    • Author(s)
      松下 雅樹
    • Organizer
      Achondroplasia Workshop
    • Place of Presentation
      後楽ホテル(岡山県岡山市)
    • Year and Date
      2015-11-21
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] meclozineは軟骨無形成症における大後頭孔および脊柱管狭窄を改善しうる2015

    • Author(s)
      松下 雅樹、鬼頭 浩史、三島 健一、杉浦 洋、長谷川 幸、北村 暁子、西田 佳弘、石黒 直樹、大野 欽司
    • Organizer
      第30回日本整形外科学会基礎学術集会
    • Place of Presentation
      富山国際会議場 ANAクラウンプラザホテル富山 富山市民プラザ(富山県富山市)
    • Year and Date
      2015-10-22
    • Related Report
      2015 Research-status Report
  • [Presentation] Meclozine has a potential effects on short stature and foramen magnum stenosis in transgenic mice with achondroplasia2015

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Kenichi Mishima, Hiroshi Sugiura, Sachi Hasegawa, Akiko Kitamura, Naoki Ishiguro, Kinji Ohno
    • Organizer
      7th International Conference on Children’s Bone Health (ICCBH)
    • Place of Presentation
      Salzburg,Austria
    • Year and Date
      2015-06-27
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research

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Published: 2015-04-16   Modified: 2019-03-29  

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