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Crosstalk of intra-cellular signaling pathway in bone formation

Research Project

Project/Area Number 18390421
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionOsaka City University

Principal Investigator

KOIKE Tatsuya  Osaka City University, 大学院・医学研究科, 准教授 (50271177)

Co-Investigator(Kenkyū-buntansha) WAKITANI Shigeyuki  大阪市立大学, 大学院・医学研究科, 准教授 (70243243)
TAKAOKA Kunio  大阪市立大学, 大学院・医学研究科, 教授 (30112048)
片桐 岳信  埼玉医科大学, 医学部, 准教授 (80245802)
Co-Investigator(Renkei-kenkyūsha) KATAGIRI Takenobu  埼玉医科大学, 医学部, 教授 (80245802)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥14,600,000 (Direct Cost: ¥12,200,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2008: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2007: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2006: ¥4,200,000 (Direct Cost: ¥4,200,000)
Keywords副甲状腺ホルモン / 骨形成因子 / 細胞内情報伝達系 / サイクリックAMP / cAMP / 骨芽細胞様細胞 / BMP / シグナル伝達 / CREB / PTH
Research Abstract

骨形成を促進する代表的サイトカインであるBMP(Bone morphogenetic protein、骨形成因子)の細胞内シグナル伝達機構をcAMPが促進することを明らかにした。この機構が遺伝子レベルにおいても成立することを明白にし、作用機序が明らかでないまま臨床応用されている副甲状腺ホルモン(PTH, Parathyroid hormone)のセカンドメッセンジャーであるcAMP系にもBMPシグナル促進効果が存在することを発見した。そして、PTHの作用の一部がBMPを介して発揮されていることを明らかにした

Report

(4 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (38 results)

All 2009 2008 2007 2006

All Journal Article (26 results) (of which Peer Reviewed: 22 results) Presentation (8 results) Book (4 results)

  • [Journal Article] RNA interference for Noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro2009

    • Author(s)
      Takayama K, Suzuki A, Manaka T, Taguchi S, Hashimoto Y, Imai Y, Wakitani S, Takaoka K
    • Journal Title

      J Bone Miner Metab, Online Feb 28

    • NAID

      10027204830

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3'2009

    • Author(s)
      Nakao Y, Koike T, Ohta Y, Manaka T, Imai Y, Takaoka K
    • Journal Title

      5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cell Bone 44

      Pages: 872-877

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway2008

    • Author(s)
      Ohta Y, Nakagawa K, ImaiY, Katagiri T, Koike T, Takaoka K
    • Journal Title

      J Bone Miner Metab 26(5)

      Pages: 478-484

    • NAID

      10024459494

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] BMP type I receptor inhibition prevents ectopic ossification in a mouse model of fibrodysplasia ossificans progressiva2008

    • Author(s)
      Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T
    • Journal Title

      Nat Med 14

      Pages: 1363-1369

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway2008

    • Author(s)
      Ohta Y, et al.
    • Journal Title

      J Bone Mineral Metab 26

      Pages: 478-484

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization2008

    • Author(s)
      Suzuki O, et al.
    • Journal Title

      Curr Med Chem 15

      Pages: 305-313

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation2008

    • Author(s)
      Mizuno Y, et al.
    • Journal Title

      Biochera Biophys Res Commun 368

      Pages: 267-272

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A unique mutation of ALK2, G356D, found in a patient with fibrodysplasia ossificans progressiva is a moderately activated BMP type I receptor2008

    • Author(s)
      Fukuda T, et al.
    • Journal Title

      Biochem Biophys Res Commun 37

      Pages: 905-909

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] BMP type l receptor inhibition prevents ectopic ossification in a mouse model of fibrodysplasia ossificans progressiva2008

    • Author(s)
      Yu PB, et al.
    • Journal Title

      Nat Med 14

      Pages: 1363-1369

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Alveolar bone regeneration of subcutaneously transplanted rat molar2008

    • Author(s)
      Hosoya A, et al.
    • Journal Title

      Bone 42

      Pages: 350-357

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Wnt/beta-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes:its possible role in joint degeneration2008

    • Author(s)
      Yuasa T, et. al.
    • Journal Title

      Lab Invest 88

      Pages: 267-74

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization2008

    • Author(s)
      Suzuki O, et. al.
    • Journal Title

      Curr.Med.Chem. 15

      Pages: 305-313

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation2008

    • Author(s)
      Mizuno Y, et. al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 368

      Pages: 267-272

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression profiles of phosphodiesterase 4D splicing variants in osteoblastic cells2008

    • Author(s)
      Nomura-Furuwatari C, et. al.
    • Journal Title

      J Bone Mineral Metab 26

      Pages: 152-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Detection of gene expression in synovium of patients with osteoarthritis using a random sequencing method2007

    • Author(s)
      Okabe T, Ohmori Y, Tanigami A, Hishigaki H, Suzuki Y, Sugano S, Kawaguchi A, Nakaya H, Wakitani S
    • Journal Title

      Acta Orthop 78

      Pages: 687-692

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] FGF23 induces expression of two isoforms of NAB2,which are corepressors of Egr-12007

    • Author(s)
      Fukuda T, et. al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 353

      Pages: 147-151

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-4 inhibition of osteoclast differentiation is stronger than that of interleukin-13 and they are equivalent for induction of osteoprotegerin production from osteoblasts2007

    • Author(s)
      Yamada A, et. al.
    • Journal Title

      Immunology 120

      Pages: 573-579

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DEAD-box helicase subunits of the Drosha complex are required for MicroRNA and rRNA processing2007

    • Author(s)
      Fukuda T, et. al.
    • Journal Title

      Nat.Cell Biol. 9

      Pages: 604-611

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Platelet-rich plasma stimulates osteoblastic differentiation in the presence of BMPs2007

    • Author(s)
      Tomoyasu A, et. al.
    • Journal Title

      Biochem.Biophys.Res.Commun. 361

      Pages: 62-67

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells2007

    • Author(s)
      Kuroda R, et. al.
    • Journal Title

      Osteoarthritis Cartilage 15

      Pages: 226-231

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Purification and identification of a BMP-like factor from bovine serum2006

    • Author(s)
      Kodaira K, Imada M, Goto M, Tomoyasu A, Fukuda T, Kamijo R, Suda T, Higashio K, and Katagiri T.
    • Journal Title

      Biochem Biophys Res Commun 345

      Pages: 1224-1231

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-22006

    • Author(s)
      Zhao B, Katagiri T, Toyoda H, Takada T, Yanai T, Fukuda T, Chung U-I, Koike T, Takaoka K, and Kamijo R.
    • Journal Title

      J Biol Chem 281

      Pages: 23246-23253

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-22006

    • Author(s)
      B.Zhao, T.Katagiri, H.Toyod, T.Takada, T.Yanai, T.Fukuda, U.Chang, T.Koike, K.Takaoka, R.Kamijo
    • Journal Title

      J Biol Chem 281

      Pages: 23246-23253

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Wnt/b-catenin signaling in chondrocyte function and cartilage matrix disruption2006

    • Author(s)
      Enomoto-Iwamoto M., Otani T., Koike T., Iwamoto M.
    • Journal Title

      Current Rheumatology Reviews 2

      Pages: 31-38

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bone morphogenetic protein activities are enhanced by 3',5'-cyclic adenosine monophosphate through suppression of Smad6 expression in osteoprogenitor cells2006

    • Author(s)
      Sugama R, Koike T., Imai Y, Nomura-Furukawa C., Takaoka K.
    • Journal Title

      Bone 38

      Pages: 206-214

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Co-ordinate expression of BMP-2, BMP receptors and Noggin in normal mouse spine2006

    • Author(s)
      Nakamura Y, Nakaya H, Saito N, Wakitani S
    • Journal Title

      J Clinical Neuroscience 13

      Pages: 250-256

    • Related Report
      2006 Annual Research Report
  • [Presentation] Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3' 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cell2009

    • Author(s)
      Nakao Y, Koike T, Ohta Y, Manaka T, Imai Y, Takaoka K.
    • Organizer
      第55回アメリカ整形外科基礎学会、ラスベガス
    • Year and Date
      2009-02-22
    • Related Report
      2008 Final Research Report
  • [Presentation] Parathyroid hormone enhances bone morphogenetic protein activity by increasing the intracellular 3', 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-El cells2009

    • Author(s)
      Nakao Y, et al.
    • Organizer
      55th Annual Meeting of the Orthopaedic Research Society
    • Place of Presentation
      Sands Expo Convention Center, Las Vegas
    • Year and Date
      2009-02-22
    • Related Report
      2008 Annual Research Report
  • [Presentation] PTHによるBMPの骨分化作用増強2008

    • Author(s)
      中尾佳裕, 他
    • Organizer
      第23回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都国際会議場、京都
    • Year and Date
      2008-10-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] Wnt/β-カテニンシグナルは関節軟骨細胞における基質分解酵素の発現を促進し変形性関節症に関与する2008

    • Author(s)
      湯浅崇仁, 他
    • Organizer
      第23回日本整形外科学会基礎学術集会
    • Place of Presentation
      京都国際会議場、京都
    • Year and Date
      2008-10-24
    • Related Report
      2008 Annual Research Report
  • [Presentation] Endogenous Cyclic Adenosine 3', 5'-Monophosphate AMP Response Element-Binding Protein (CREB) Signaling Enhances Smad-Mediated Bone Morphogenetic Protein (BMP) Signaling. Journal of Bone and Mineral Research 22 : S3912007

    • Author(s)
      Ohta Y, Nakagawa K, Imai Y, Katagiri T, Koike T, Takaoka K
    • Organizer
      第29回アメリカ骨ミネラル代謝学会
    • Place of Presentation
      ホノルル
    • Year and Date
      2007-09-19
    • Related Report
      2008 Final Research Report
  • [Presentation] Endogenous cyclic adenosine 3',5'-monophosphate response element-binding prote in(CREB)signaling enhances smad-mediated bone morphogenetic protein(BMP)signaling2007

    • Author(s)
      Ohta Y, et. al.
    • Organizer
      29th ASBMR Annual Meeting
    • Place of Presentation
      Honolulu,Hawaii
    • Year and Date
      2007-09-19
    • Related Report
      2007 Annual Research Report
  • [Presentation] Cyclic AMP Accelerates BMP Signaling by Enhancing the Transcriptional Activity of BMP Responsive Element through Cyclic AMP Responsive Element. Journal of Bone and Mineral Research 21 : S1262006

    • Author(s)
      Ohta Y, Nakagawa K, Imai Y, Nomura C, Katagiri T, Koike T, Takaoka K
    • Organizer
      第28回アメリカ骨ミネラル代謝学会
    • Place of Presentation
      フィラデルフィア
    • Year and Date
      2006-09-16
    • Related Report
      2008 Final Research Report
  • [Presentation] Enhancement of BMP signaling by cyclic AMP : Its role and mechanism. Bone 38 : S172006

    • Author(s)
      Ohta Y, Nakagawa K, Imai Y, Nomura C, Katagiri T, Koike T, Takaoka K
    • Organizer
      ダボス骨ワークショップ
    • Place of Presentation
      ダボス
    • Year and Date
      2006-03-18
    • Related Report
      2008 Final Research Report
  • [Book] The TGF-b Superfamily Monograph (Miyazono, K. and Derynck, R., editors.) Cold Spring Harbor Press2008

    • Author(s)
      Katagiri T, et. al.
    • Total Pages
      520
    • Publisher
      The bone morphogenetic proteins
    • Related Report
      2007 Annual Research Report
  • [Book] New Frontiers in Regenerative Medicine (M.Kusano and S.Shioda Eds.) Springer2007

    • Author(s)
      Zhao B, et. al.
    • Total Pages
      154
    • Publisher
      Heparin enhances BMP activity by maintaining high levels of nuclear phosphorylated Smad1/5/8
    • Related Report
      2007 Annual Research Report
  • [Book] New Frontiers in Regenerative Medicine(M. Kusano and S. Shioda Eds.)(Springer)2007

    • Author(s)
      B.Zhao, T.Katagiri, H.Toyoda, T.Takada, T.Koike, K.Takaoka, R.Kamijo
    • Publisher
      Heparin enhances BMP activity by maintaining high levels of nuclear phophorylated Smad1/5/8
    • Related Report
      2006 Annual Research Report
  • [Book] Heparin enhances BMP activity by maintaining high levels of nuclear phosphorylated Smad1/5/82006

    • Author(s)
      Zhao B, Katagiri T, Toyoda H, Takada T, Koike T, Takaoka K, and Kamijo R. eds. Kusano M and Shioda S Springer, Japan
    • Publisher
      Frontiers in Regenerative Medicine
    • Related Report
      2008 Final Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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