Crosstalk of intra-cellular signaling pathway in bone formation

• Project/Area Number: 18390421
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Osaka 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: ¥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

Research Products

• [Journal Article] RNA interference for Noggin enhances the biological activity of bone morphogenetic proteins in vivo and in vitro (2009)
  • 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
  • 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
  • Peer Reviewed
• [Journal Article] Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway (2008)
  • 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
  • Peer Reviewed
• [Journal Article] BMP type I receptor inhibition prevents ectopic ossification in a mouse model of fibrodysplasia ossificans progressiva (2008)
  • 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
  • Peer Reviewed
• [Journal Article] Cyclic AMP enhances Smad-mediated BMP signaling through PKA-CREB pathway (2008)
  • Author(s): Ohta Y, et al.
  • Journal Title: J Bone Mineral Metab 26 Pages: 478-484
  • Peer Reviewed
• [Journal Article] Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization (2008)
  • Author(s): Suzuki O, et al.
  • Journal Title: Curr Med Chem 15 Pages: 305-313
  • Peer Reviewed
• [Journal Article] miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation (2008)
  • Author(s): Mizuno Y, et al.
  • Journal Title: Biochera Biophys Res Commun 368 Pages: 267-272
  • 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 receptor (2008)
  • Author(s): Fukuda T, et al.
  • Journal Title: Biochem Biophys Res Commun 37 Pages: 905-909
  • Peer Reviewed
• [Journal Article] BMP type l receptor inhibition prevents ectopic ossification in a mouse model of fibrodysplasia ossificans progressiva (2008)
  • Author(s): Yu PB, et al.
  • Journal Title: Nat Med 14 Pages: 1363-1369
  • Peer Reviewed
• [Journal Article] Alveolar bone regeneration of subcutaneously transplanted rat molar (2008)
  • Author(s): Hosoya A, et al.
  • Journal Title: Bone 42 Pages: 350-357
  • Peer Reviewed
• [Journal Article] Wnt/beta-catenin signaling stimulates matrix catabolic genes and activity in articular chondrocytes:its possible role in joint degeneration (2008)
  • Author(s): Yuasa T, et. al.
  • Journal Title: Lab Invest 88 Pages: 267-74
  • Peer Reviewed
• [Journal Article] Bone regeneration by synthetic octacalcium phosphate and its role in biological mineralization (2008)
  • Author(s): Suzuki O, et. al.
  • Journal Title: Curr.Med.Chem. 15 Pages: 305-313
  • Peer Reviewed
• [Journal Article] miR-125b inhibits osteoblastic differentiation by down-regulation of cell proliferation (2008)
  • Author(s): Mizuno Y, et. al.
  • Journal Title: Biochem.Biophys.Res.Commun. 368 Pages: 267-272
  • Peer Reviewed
• [Journal Article] Expression profiles of phosphodiesterase 4D splicing variants in osteoblastic cells (2008)
  • Author(s): Nomura-Furuwatari C, et. al.
  • Journal Title: J Bone Mineral Metab 26 Pages: 152-8
  • Peer Reviewed
• [Journal Article] Detection of gene expression in synovium of patients with osteoarthritis using a random sequencing method (2007)
  • 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
  • Peer Reviewed
• [Journal Article] FGF23 induces expression of two isoforms of NAB2,which are corepressors of Egr-1 (2007)
  • Author(s): Fukuda T, et. al.
  • Journal Title: Biochem.Biophys.Res.Commun. 353 Pages: 147-151
  • 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 osteoblasts (2007)
  • Author(s): Yamada A, et. al.
  • Journal Title: Immunology 120 Pages: 573-579
  • Peer Reviewed
• [Journal Article] DEAD-box helicase subunits of the Drosha complex are required for MicroRNA and rRNA processing (2007)
  • Author(s): Fukuda T, et. al.
  • Journal Title: Nat.Cell Biol. 9 Pages: 604-611
  • Peer Reviewed
• [Journal Article] Platelet-rich plasma stimulates osteoblastic differentiation in the presence of BMPs (2007)
  • Author(s): Tomoyasu A, et. al.
  • Journal Title: Biochem.Biophys.Res.Commun. 361 Pages: 62-67
  • Peer Reviewed
• [Journal Article] Treatment of a full-thickness articular cartilage defect in the femoral condyle of an athlete with autologous bone-marrow stromal cells (2007)
  • Author(s): Kuroda R, et. al.
  • Journal Title: Osteoarthritis Cartilage 15 Pages: 226-231
  • Peer Reviewed
• [Journal Article] Purification and identification of a BMP-like factor from bovine serum (2006)
  • 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
  • Peer Reviewed
• [Journal Article] Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2 (2006)
  • 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
  • Peer Reviewed
• [Journal Article] Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2 (2006)
  • 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
• [Journal Article] Wnt/b-catenin signaling in chondrocyte function and cartilage matrix disruption (2006)
  • Author(s): Enomoto-Iwamoto M., Otani T., Koike T., Iwamoto M.
  • Journal Title: Current Rheumatology Reviews 2 Pages: 31-38
• [Journal Article] Bone morphogenetic protein activities are enhanced by 3',5'-cyclic adenosine monophosphate through suppression of Smad6 expression in osteoprogenitor cells (2006)
  • Author(s): Sugama R, Koike T., Imai Y, Nomura-Furukawa C., Takaoka K.
  • Journal Title: Bone 38 Pages: 206-214
• [Journal Article] Co-ordinate expression of BMP-2, BMP receptors and Noggin in normal mouse spine (2006)
  • Author(s): Nakamura Y, Nakaya H, Saito N, Wakitani S
  • Journal Title: J Clinical Neuroscience 13 Pages: 250-256
• [Presentation] Parathyroid hormone enhances bone morphogenetic protein activity by increasing intracellular 3' 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-E1 cell (2009)
  • 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
• [Presentation] Parathyroid hormone enhances bone morphogenetic protein activity by increasing the intracellular 3', 5'-cyclic adenosine monophosphate accumulation in osteoblastic MC3T3-El cells (2009)
  • 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
• [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
• [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
• [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 : S391 (2007)
  • 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
• [Presentation] Endogenous cyclic adenosine 3',5'-monophosphate response element-binding prote in(CREB)signaling enhances smad-mediated bone morphogenetic protein(BMP)signaling (2007)
  • Author(s): Ohta Y, et. al.
  • Organizer: 29th ASBMR Annual Meeting
  • Place of Presentation: Honolulu,Hawaii
  • Year and Date: 2007-09-19
• [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 : S126 (2006)
  • 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
• [Presentation] Enhancement of BMP signaling by cyclic AMP : Its role and mechanism. Bone 38 : S17 (2006)
  • 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
• [Book] The TGF-b Superfamily Monograph (Miyazono, K. and Derynck, R., editors.) Cold Spring Harbor Press (2008)
  • Author(s): Katagiri T, et. al.
  • Total Pages: 520
  • Publisher: The bone morphogenetic proteins
• [Book] New Frontiers in Regenerative Medicine (M.Kusano and S.Shioda Eds.) Springer (2007)
  • Author(s): Zhao B, et. al.
  • Total Pages: 154
  • Publisher: Heparin enhances BMP activity by maintaining high levels of nuclear phosphorylated Smad1/5/8
• [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
• [Book] Heparin enhances BMP activity by maintaining high levels of nuclear phosphorylated Smad1/5/8 (2006)
  • 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