Elucidation of physiological role of the bone formation potentiator contained in platelet.

• Project/Area Number: 21890243
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Orthopaedic surgery
• Research Institution: Saitama Medical University
• Principal Investigator: OHTE Satoshi Saitama Medical University, 医学部, 助教 (00547979)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,587,000 (Direct Cost: ¥1,990,000、Indirect Cost: ¥597,000); Fiscal Year 2010: ¥1,222,000 (Direct Cost: ¥940,000、Indirect Cost: ¥282,000); Fiscal Year 2009: ¥1,365,000 (Direct Cost: ¥1,050,000、Indirect Cost: ¥315,000)
• Keywords: 骨代謝 / 血小板 / Bone morphogenetic protein / Smad / 骨形成 / タンパク質 / 細胞・組織 / 骨芽細胞

Research Abstract

The aim of this study is to elucidate the physiological role of the bone formation potentiator contained in platelet. As a result, it became clear that this protein increase the activity of bone morphogenetic protein (BMP), which is the cytokine induce ectopic bone formation in muscular tissue, in vitro and in vivo. Our findings suggest that this protein will become new medicine of bone formation.

Research Products

• [Journal Article] A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H (2011)
  • Author(s): Ohte S, Shin M, Sasanuma H, Yoneyama K, Akita M, Ikebuchi K, Jimi E, Maruki Y, Matsuoka M, Namba A, Tomoda H, Okazaki Y, Ohtake A, Oda H, Owan I, Yoda T, Furuya H, Kamizono J, Kitoh H, Nakashima Y, Susami T, Haga N, Komori T, Katagiri T
  • Journal Title: Biochem Biophys Res Commun. 407 Pages: 213-218
  • Peer Reviewed
• [Journal Article] Suppression of BMP-Smad signaling axis-induced osteoblastic differentiation by small C-terminal domain phosphatase 1, a Smad phosphatase. (2011)
  • Author(s): Kokabu S, Ohte S, Sasanuma H, Shin M, Yoneyama K, Murata E, Kanomata K, Nojima J, Ono Y, Yoda T, Fukuda T, Katagiri T
  • Journal Title: Mol Endocrinol. 25 Pages: 474-481
  • Peer Reviewed
• [Journal Article] A novel mutation of ALK2, L196P, found in the most benign case of fibrodysplasia ossificans progressiva activates BMP-specific intracellular signaling equivalent to a typical mutation, R206H. (2011)
  • Author(s): Ohte S
  • Journal Title: Biochem Biophys Res Commun Volume: 407(1) Pages: 213-218
  • Peer Reviewed
• [Journal Article] Suppression of BMP-Smad signaling axis-induced osteoblastic differentiation by small C-terminal domain phosphatase 1, a Smad phosphatase. (2011)
  • Author(s): Kokabu S
  • Journal Title: Mol Endcrinol Volume: 25(3) Pages: 474-481
  • Peer Reviewed
• [Journal Article] Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3beta-dependent and beta-catenin-independent mechanism. (2010)
  • Author(s): Fukuda T, Kokabu S, Ohte S, Sasanuma H, Kanomata K, Yoneyama K, Kato H, Akita M, Oda H, Katagiri T
  • Journal Title: Differentiation. 80 Pages: 46-52
  • Peer Reviewed
• [Journal Article] Dual roles of smad proteins in the conversion from myoblasts to osteoblastic cells by bone morphogenetic proteins. (2010)
  • Author(s): Nojima J, Kanomata K, Takada Y, Fukuda T, Kokabu S, Ohte S, Takada T, Tsukui T, Yamamoto TS, Sasanuma H, Yoneyama K, Ueno N, Okazaki Y, Kamijo R, Yoda T, Katagiri T
  • Journal Title: J Biol Chem 285 Pages: 15577-15586
  • Peer Reviewed
• [Journal Article] Protein phosphatase magnesium-dependent 1A-mediated inhibition of BMP signaling is independent of Smad dephosphorylation. (2010)
  • Author(s): Kokabu S, Nojima J, Kanomata K, Ohte S, Yoda T, Fukuda T, Katagiri T
  • Journal Title: J Bone Miner Res. 25 Pages: 653-660
  • Peer Reviewed
• [Journal Article] Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3beta-dependent and beta-catenin-independent mechanism. (2010)
  • Author(s): Fukuda T
  • Journal Title: Differentiation Volume: 80(1) Pages: 46-52
  • Peer Reviewed
• [Journal Article] Dual roles of smad proteins in the conversion from myoblasts to osteoblastic cells by bone morphogenetic proteins. (2010)
  • Author(s): Nojima J
  • Journal Title: J Biol Chem Volume: 285(20) Pages: 15577-15586
  • Peer Reviewed
• [Journal Article] Nosokomycins, new antibiotics discovered in an in vivo-mimic infection model using silkworm larvae I : Fermentation, isolation and biological properties. (2010)
  • Author(s): Uchida R
  • Journal Title: J Antibiot Volume: 63(4) Pages: 151-155
  • Peer Reviewed
• [Journal Article] Protein phosphatase magnesium-dependent 1A-mediated inhibition of BMP signaling is independent of Smad-dephosphorylation (2010)
  • Author(s): Kokabu S
  • Journal Title: J Bone Miner Res (In press)
  • Peer Reviewed
• [Presentation] 新規Smad結合因子Zranb2はBMPシグナル抑制因子である (2010)
  • Author(s): 大手聡
  • Organizer: 第8回 RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2010-11-03
• [Presentation] 骨芽細胞分化におけるBMPとWntシグナルの相互作用の解明 (2010)
  • Author(s): 笹沼寛樹
  • Organizer: 第8回 RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2010-11-03
• [Presentation] SCP1はBMP誘導性の骨芽細胞分化においてSmadの下流因子を抑制する (2010)
  • Author(s): 進正史
  • Organizer: 第8回 RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2010-11-03
• [Presentation] Identification of Zranb2, a novel R-Smads binding protein, as a suppressor of BMP signaling. (2010)
  • Author(s): Satoshi Ohte, Shoichiro Kokabu, Toru Fukuda,, Shunichiro Iemura, Hiroki Sasanuma, Katsumi Yoneyama, Masashi Shin, Eijiro Jimi, Toru Natsume, Takenobu Katagiri
  • Organizer: 2010 ASBMR Annual Meeting
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2010-10-17
• [Presentation] Platelet Factor 4 is a novel potentiator of BMP-induced osteoblastic differentiation and bone formation. (2010)
  • Author(s): Takenobu Katagiri, Toru Fukuda, Akihiro Tomoyasu, Masaaki Goto, Kunihiko Kodaira, Shoichiro Kokabu, Satoshi Ohte, 他18名
  • Organizer: 2010 ASBMR Annual Meeting
  • Place of Presentation: トロント(カナダ)
  • Year and Date: 2010-10-17
• [Presentation] PPM1A and SCP1, Smad phosphatases, inhibits BMP-induced osteoblastic differentiation by different molecular mechanisms (2010)
  • Author(s): Katagiri T
  • Organizer: 8^<th> International BMP Conference
  • Place of Presentation: ルーベン(ベルギー)
  • Year and Date: 2010-09-17
• [Presentation] Identification and characterization of a nuclear protein as a co-suppressor of BMP-regulated R-Smads. (2010)
  • Author(s): Satoshi Ohte, Shoichiro Kokabu, Toru Fukuda, Shunichiro Iemura, Hiroki Sasanuma, Katsumi Yoneyama, Masashi Shin, Eijiro Jimi, Toru Natsume, Takenobu Katagiri
  • Organizer: 8th International BMP Conference
  • Place of Presentation: ルーベン(ベルギー)
  • Year and Date: 2010-09-15
• [Presentation] Identification and characterization of a nuclear protein as a co-suppressor of BMP-regulated R-Smads (2010)
  • Author(s): Ohte S
  • Organizer: 8^<th> International BMP Conference
  • Place of Presentation: ルーベン(ベルギー)
  • Year and Date: 2010-09-15
• [Presentation] 血小板第4因子は血中の新規BMP活性促進因子である (2010)
  • Author(s): 片桐岳信
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-22
• [Presentation] 新規R-Smad結合分子ZRANB2のBMPシグナル阻害活性 (2010)
  • Author(s): 大手聡、古株彰一郎、福田亨、笹沼寛樹、米山克美、進正史、自見英治郎、片桐岳信
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] 新規R-Smad結合因子ZRANB2のBMPシグナル阻害活性 (2010)
  • Author(s): 大手聡
  • Organizer: 第28回日本骨代謝学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-21
• [Presentation] 骨芽細胞におけるSmadとRunx2のクロストーク (2009)
  • Author(s): 大手聡、福田亨、古株彰一郎、片桐岳信
  • Organizer: 第7回RCGMフロンティアシンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2009-11-03
• [Presentation] 骨芽細胞における Smad とRunx2のクロストーク (2009)
  • Author(s): 大手聡
  • Organizer: 第7回RCGMフロンティアシンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2009-11-03
• [Presentation] Smad1の骨芽細胞分化誘導活性はC末端とリンカー領域のリン酸化により制御される (2009)
  • Author(s): 古株彰一郎
  • Organizer: 第7回RCGMフロンティアシンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2009-11-03
• [Presentation] Fibrodysplasia ossificans progressiva(FOP)で同定された10種類のALK2変異体の機能解析 (2009)
  • Author(s): 福田亨
  • Organizer: 第7回RCGMフロンティアシンポジウム
  • Place of Presentation: 埼玉
  • Year and Date: 2009-11-03
• [Presentation] 筋組織内に異所性骨化を生じる遺伝性難病(Fibrodysplasia Ossificans Progressiva) (2009)
  • Author(s): 福田亨
  • Organizer: 運動器科学研究会
  • Place of Presentation: 東京
  • Year and Date: 2009-09-18
• [Presentation] Smad1のリン酸化・脱リン酸化による骨芽細胞分化誘導の制御 (2009)
  • Author(s): 古株彰一郎
  • Organizer: 第16回BMP研究会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-27
• [Presentation] Fibrodysplasia ossificans progressiva(FOP)で新たに同定されたALK2変異体の解析 (2009)
  • Author(s): 福田亨
  • Organizer: 第16回BMP研究会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-27
• [Presentation] Smad C末端のホスファターゼPPM1AとSCP1はリンカー領域のMAPKリン酸化部位を介してBMPシグナルを抑制する (2009)
  • Author(s): 古株彰一郎
  • Organizer: 第27回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-25
• [Presentation] Fibrodysplasia ossificans progressiva(FOP)で同定されたALK2変異体の解析 (2009)
  • Author(s): 福田亨
  • Organizer: 第27回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-07-25
• [Presentation] R-Smad のホスファターゼPPM1AによるBMP活性の抑制には Smad の脱リン酸化に依存しない分解が重要である (2009)
  • Author(s): 古株彰一郎
  • Organizer: 第8回松本ボーンフォーラム
  • Place of Presentation: 長野
  • Year and Date: 2009-05-08
• [Presentation] Functional Analysis of Mutant ALK2 Receptors Found in Fibrodysplasia ossificans progressiva(FOP) (2009)
  • Author(s): 福田亨
  • Organizer: 31^<st> ASBMR(American Society for Bone and Mineral Research)annual meeting
  • Place of Presentation: 米国コロラド州
• [Presentation] PPM1A and SCP1 suppress BMP activity via novel mechanism in independent of Smad C-terminal dephosphorylation (2009)
  • Author(s): 古株彰一郎
  • Organizer: 31^<st> ASBMR(American Society for Bone and Mineral Research)annual meeting
  • Place of Presentation: 米国コロラド州
• [Remarks] ホームページ等
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