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Bone regeneration using culture-expanded bone marrow cells-Efficacy of Runx2-activating drugs-

Research Project

Project/Area Number 24592230
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

HIROSHI Kitoh  名古屋大学, 医学(系)研究科(研究院), 准教授 (40291174)

Co-Investigator(Kenkyū-buntansha) 金子 浩史  名古屋大学, 医学(系)研究科(研究院), 助教 (60566975)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsRunx2 / ランソプラゾール / 骨組織再生 / 培養骨髄細胞 / 骨芽細胞 / 骨形成 / 骨形成促進 / drug repositioning
Outline of Final Research Achievements

We screened for drugs that activate the Runx2 promoter and identified that lansoprazole, a proton pump inhibitor, upregulated the Runx2 activity. Lansoprazole elevated expression levels of Runx2 mRNA and protein in osteoblast-lineage cells in a dose-dependent manner. Lansoprazole exerted an increase of ALP and Osterix activities in osteoblast-lineage cells. Lansoprazole accelerated the matrix calcium deposition in human bone marrow derived osteoprogenitors. Systemic administration of lansoprazole to a rat fracture model increased osteoblastic parameters and facilitated fracture healing. We propose that lansoprazole holds promise as a therapeutic agent for bone regeneration at fracture sites.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (38 results)

All 2014 2013 2012

All Journal Article (22 results) (of which Peer Reviewed: 22 results,  Open Access: 6 results) Presentation (15 results) (of which Invited: 4 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Benign prenatal hypophosphatasia: a treatable disease not to be missed.2014

    • Author(s)
      Matsushita M, Kitoh H, Michigami T, Tachikawa K, Kaneko H, Mishima K, Ishiguro N.
    • Journal Title

      Ped Radiol

      Volume: 44(3) Issue: 3 Pages: 340-343

    • DOI

      10.1007/s00247-013-2805-z

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Biodistribution of locally or systemically transplanted osteoblast-like cells.2014

    • Author(s)
      Y.T. Okabe, T. Kondo, K. Mishima, Y. Hayase, K. Kato, M. Mizuno, N. Ishiguro and H. Kitoh
    • Journal Title

      Bone Joint Res

      Volume: 3 Issue: 3 Pages: 76-81

    • DOI

      10.1302/2046-3758.33.2000257

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radiographic characteristics of the hand and cervical spine in fibrodysplasia ossificans progressiva2014

    • Author(s)
      Mishima K, Kitoh H, Haga N, Nakashima Y, Kamizono J, Katagiri T, Susami T, Matsushita M, Ishiguro N.
    • Journal Title

      Intractable & Rare Diseases Research

      Volume: 3 Issue: 2 Pages: 46-51

    • DOI

      10.5582/irdr.2014.01009

    • NAID

      130005008088

    • ISSN
      2186-361X, 2186-3644
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A case of severe proximal focal femoral deficiency with overlapping phenotypes of Al-Awadi-Raas-Rothschild syndrome and Fuhrmann syndrom2014

    • Author(s)
      Matsushita M, Kitoh H, Mishima K, Nishida Y, Ishiguro N
    • Journal Title

      Ped Radiol

      Volume: 44 Issue: 12 Pages: 1617-1619

    • DOI

      10.1007/s00247-014-3013-1

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Early and late fracture following extensive limb lengthening in achondroplasia and hypochondroplasia.2014

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

      Bone Joint J

      Volume: 96-B(9) Issue: 9 Pages: 1269-1273

    • DOI

      10.1302/0301-620x.96b9.33840

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors associated with an unfavourable outcome after Salter innominate osteotomy in patients with unilateral developmental dysplasia of the hip: Does occult dysplasia of the contralateral hip affect the outcome?2014

    • Author(s)
      Kaneko H, Kitoh H, Mishima K, Matsushita M, Izumi K, Naoki Ishiguro, Hattori T
    • Journal Title

      Bone Joint J

      Volume: 96 Issue: 10 Pages: 1419-1423

    • DOI

      10.1302/0301-620x.96b10.34263

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations in PCYT1A, encoding a key regulator of phosphatidylcholine metabolism, cause spondylometaphyseal dysplasia with cone-rod dystrophy.2014

    • Author(s)
      Hoover-Fong J, Sobreira N, Jurgens J, Modaff P, Blout C, Moser A, Kim OH, Cho TJ, Cho SY, Kim SJ, Jin DK, Kitoh H, Park WY, Ling H, Hetrick KN, Doheny KF, Valle D, Pauli RM.
    • Journal Title

      Am J Hum Genet

      Volume: 94(1) Issue: 1 Pages: 105-112

    • DOI

      10.1016/j.ajhg.2013.11.018

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel in-frame deletion of the RUNX2 gene causes a classic form of cleidocranial dysplasia2013

    • Author(s)
      Mastushita M., Kitoh H., Kaneko H., Mishima K., Itoh Y., Tokita Y., Ishiguro N.
    • Journal Title

      J Bone Miner Metab

      Volume: 未定 Issue: 1 Pages: 96-99

    • DOI

      10.1007/s00774-013-0456-7

    • Related Report
      2014 Annual Research Report 2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinically applicable antianginal agents suppress osteoblastic transformation of myogenic cells and heterotopic ossifications in mice2013

    • Author(s)
      Yamamoto R, Matsushita M, Kitoh H, Masuda A, Ito M, Katagiri T, Kawai T, Ishiguro N, Ohno K
    • Journal Title

      J Bone Miner Metab

      Volume: 31 Pages: 26-33

    • DOI

      10.1007/s00774-012-0380-2

    • NAID

      10031168834

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Orthopaedic manifestations and diagnostic clues in children with Guillain-Barré syndrome.2013

    • Author(s)
      Matsushita M, Kitoh H, Itomi K, Kitakoji T, Iwata K, Mishima K, Ishiguro N, Hattori T
    • Journal Title

      J Child Orthop

      Volume: 7 Issue: 3 Pages: 177-182

    • DOI

      10.1007/s11832-012-0475-2

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic factors for trochanteric overgrowth after containment treatment in Legg-Calvé-Perthes disease.2013

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

      J Pediatr Orthop B

      Volume: 22 Issue: 5 Pages: 432-436

    • DOI

      10.1097/bpb.0b013e32835f585b

    • Related Report
      2013 Research-status Report 2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutations in B3GALT6 which Encodes a Glycosaminoglycan Linker Region Enzyme Cause a Spectrum of Skeletal and Connective Tissue Disorders2013

    • Author(s)
      Masahiro Nakajima, Shuji Mizumoto et al.
    • Journal Title

      American Journal of Human Genetics

      Volume: in press Issue: 6 Pages: 927-934

    • DOI

      10.1016/j.ajhg.2013.04.003

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Long-term outcome of gradual reduction using overhead traction for developmental dysplasia of the hip over 6 months of age.2013

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

      J Pediatr Orthop.

      Volume: 33(6) Issue: 6 Pages: 628-34

    • DOI

      10.1097/bpo.0b013e31829b2d8b

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A comparative study of blade plate fixation and external fixation in osteotomies for slipped capital femoral epiphysis.2013

    • Author(s)
      Kitoh H, Kitakoji T, Hattori T, Kaneko H, Mishima K, Matsushita M, Ishiguro N.
    • Journal Title

      J Pediatr Orthop B.

      Volume: 22(6) Issue: 6 Pages: 542-7

    • DOI

      10.1097/bpb.0b013e3283637070

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel SOX9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome2013

    • Author(s)
      Matsushita M, Kitoh H, Kaneko H, Mishima K, Kadono I, Ishiguro N, Nishmura G
    • Journal Title

      Am J Med Genet A

      Volume: 161 Issue: 10 Pages: 2528-2534

    • DOI

      10.1002/ajmg.a.36134

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.2013

    • Author(s)
      Matsushita, M., Kitoh, H., Ohkawara, B., Mishima, K., Kaneko, H., Ito, M., Masuda, A., Ishiguro, N. and Ohno, K.
    • Journal Title

      PLOS ONE

      Volume: 8(12) Issue: 12 Pages: 81569-81569

    • DOI

      10.1371/journal.pone.0081569

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Perhexiline maleate in the treatment of fibrodysplasia ossificans progressiva: an open-labeled clinical trial.2013

    • Author(s)
      Kitoh H, Achiwa M, Kaneko H, Mishima K, Matsushita M, Kadono I, Horowitz JD, Sallustio BC, Ohno K, Ishiguro N.
    • Journal Title

      Orphanet J Rare Dis.

      Volume: 8 Issue: 1 Pages: 163-163

    • DOI

      10.1186/1750-1172-8-163

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Mutations in B3GALT6 which encodes a glycosaminoglycan linker region enzyme cause a spectrum of skeletal and connective tissue disorders2013

    • Author(s)
      Nakajima M, Mizumoto S, Miyake N, Kogawa R, Iida A, Ito H, Kitoh H, et al
    • Journal Title

      Am J Hum Genet

      Volume: in press

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Novel compound heterozygous mutations in the cathepsin K gene in Japanese female siblings with pyknodysostosis2012

    • Author(s)
      Matsushita M, Kitoh H, Kaneko H, Mishima K, Itoh Y, Hattori T, Ishiguro N
    • Journal Title

      Mol Syndromol

      Volume: (in press)(未定) Issue: 6 Pages: 254-258

    • DOI

      10.1159/000336581

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Chondroblastoma of the femoral neck as a cause of hip synovitis2012

    • Author(s)
      Kaneko H, Kitoh H, Wasa J, Nishida Y, Ishiguro N
    • Journal Title

      J Pediatr Orthop B

      Volume: 21 Issue: 2 Pages: 179-182

    • DOI

      10.1097/bpb.0b013e3283484c31

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Isolated bifid rib: Clinical and radiological findings in children.2012

    • Author(s)
      Kaneko H, Kitoh H, Mabuchi A, Mishima K, Matsushita M, Ishiguro N.
    • Journal Title

      Pediatr Int

      Volume: 54 Issue: 6 Pages: 820-823

    • DOI

      10.1111/j.1442-200x.2012.03672.x

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] The biomechanical effect of the sensomotor insole on a pediatric intoeing gait2012

    • Author(s)
      Mabuchi A, Kitoh H, Kaneko H, Inoue M, Hayashi M, Ishiguro N, Suzuki N
    • Journal Title

      ISRN Orthop

      Volume: 2012 Pages: 1-5

    • DOI

      10.5402/2012/396718

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 先天性股関節脱臼に対する選択的リーメンビューゲル法による短期治療成績2014

    • Author(s)
      鬼頭浩史、三島健一、松下雅樹、杉浦洋、長谷川幸、北村暁子、石黒直樹
    • Organizer
      第25回日本小児整形外科学会
    • Place of Presentation
      ヒルトン東京ベイ(千葉県浦安市)
    • Year and Date
      2014-11-27 – 2014-11-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 骨髄幹細胞を用いた骨延長術2014

    • Author(s)
      鬼頭浩史、三島健一、松下雅樹、杉浦洋、石黒直樹
    • Organizer
      第87回日本整形外科学会
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場、神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2014-05-22 – 2014-05-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 培養骨髄細胞とPRPの移植を併用した骨延長術2014

    • Author(s)
      鬼頭浩史、三島健一、松下雅樹、杉浦洋、石黒直樹
    • Organizer
      第87回日本整形外科学会
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場、神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2014-05-22 – 2014-05-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 下肢骨延長後の骨折に関連する因子2014

    • Author(s)
      鬼頭浩史、金子浩史、三島健一、松下雅樹、西田佳弘、石黒直樹
    • Organizer
      第87回日本整形外科学会
    • Place of Presentation
      神戸ポートピアホテル、神戸国際展示場、神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2014-05-22 – 2014-05-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Early and late fracture following lower limb lengthening2014

    • Author(s)
      Hiroshi Kitoh, Hiroshi Kaneko, Kenichi Mishima, Masaki Matsushita, Naoki Ishiguro
    • Organizer
      Annual meeting of Pediatric Orthopedic Society of North America
    • Place of Presentation
      Los Angeles, USA
    • Year and Date
      2014-04-30 – 2014-05-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 整形外科common diseasetと骨系統疾患2014

    • Author(s)
      鬼頭浩史
    • Organizer
      第122回中部日本整形外科災害外科学会
    • Place of Presentation
      岡山コンベンションセンター(岡山県岡山市)
    • Year and Date
      2014-04-11
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Long-term outcome of gradual reduction with overhead traction for developmental dysplasia of the hip in children over six months of age2013

    • Author(s)
      Hiroshi Kaneko, Hiroshi Kitoh, Kenichi Mishima, Masaki Matsushita, Naoki Ishguro
    • Organizer
      Annual meeting of Pediatric Orthopedic Society of North America
    • Place of Presentation
      Toronto(カナダ)
    • Related Report
      2013 Research-status Report
  • [Presentation] A novel Sox9 H169Q mutation in a family with overlapping phenotype of mild campomelic dysplasia and small patella syndrome2013

    • Author(s)
      Hiroshi Kaneko, Hioroshi Kitoh, Kenichi Mishima, Masaki Matsushita, Naoki Ishiguro
    • Organizer
      International Skeletal Dysplasia Meeting
    • Place of Presentation
      Bologna(イタリア)
    • Related Report
      2013 Research-status Report
  • [Presentation] Meclozine facilitates chondrocyte proliferation and differentiation by attenuating abnormally activated fibroblast growth factor receptor 3 (FGFR3) signaling in achondroplasia2013

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Hiroshi Kaneko, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno
    • Organizer
      International Skeletal Dysplasia Meeting
    • Place of Presentation
      Bologna(イタリア)
    • Related Report
      2013 Research-status Report
  • [Presentation] Potential clinical application of meclizine, an anti-histamine drug, for short stature in FGFR3-related skeletal dysplasias2013

    • Author(s)
      Masaki Matsushita, Hiroshi Kitoh, Hiroshi Kaneko, Kenichi Mishima, Naoki Ishiguro, Kinji Ohno
    • Organizer
      第24回日本小児整形外科学会
    • Place of Presentation
      パシフィコ横浜(横浜市)
    • Related Report
      2013 Research-status Report
  • [Presentation] 先天性股関節脱臼に対する新しい適応を用いたリーメンビューゲルによる短期治療成績2012

    • Author(s)
      鬼頭浩史、金子浩史、松下雅樹、石黒直樹
    • Organizer
      第85回日本整形外科学会
    • Place of Presentation
      国立京都国際会館、グランドプリンスホテル京都(京都市左京区)
    • Related Report
      2012 Research-status Report
  • [Presentation] 軟骨無形成症に対する治療の展望2012

    • Author(s)
      鬼頭浩史
    • Organizer
      第85回日本整形外科学会
    • Place of Presentation
      国立京都国際会館、グランドプリンスホテル京都(京都市左京区)
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] 先天性股関節脱臼保存治療後の臼蓋発育についてー幼児期の補正手術の適応を再考するー2012

    • Author(s)
      鬼頭浩史、金子浩史、三島健一、松下雅樹、石黒直樹
    • Organizer
      第51回日本小児股関節研究会
    • Place of Presentation
      ホテルスプリングス幕張(千葉市美浜区)
    • Related Report
      2012 Research-status Report
  • [Presentation] ヒト骨髄由来間葉系幹細胞の細胞増殖能および骨芽細胞分化能2012

    • Author(s)
      鬼頭浩史、金子浩史、三島健一、松下雅樹、石黒直樹
    • Organizer
      第23回日本小児整形外科学会
    • Place of Presentation
      九州大学医学部百年講堂(福岡市東区)
    • Related Report
      2012 Research-status Report
  • [Presentation] 進行性骨化性線維異形成症に対するマレイン酸ペルヘキシリンの治療経験2012

    • Author(s)
      鬼頭浩史、金子浩史、三島健一、松下雅樹、石黒直樹
    • Organizer
      第24回日本整形外科学会骨系統疾患研究会
    • Place of Presentation
      九州大学医学部百年講堂(福岡市東区)
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 骨形成促進剤及びその用途2012

    • Inventor(s)
      大野欽司、石黒直樹、鬼頭浩史、三島健一
    • Industrial Property Rights Holder
      大野欽司、石黒直樹、鬼頭浩史、三島健一
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2011-185306
    • Filing Date
      2012-08-23
    • Related Report
      2012 Research-status Report
    • Overseas

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Published: 2013-05-31   Modified: 2019-07-29  

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