Molecular mechanisms of regulation in locomotive tissues

2011 Fiscal Year Final Research Report

• Project/Area Number: 21390423
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Saitama Medical University
• Principal Investigator: KATAGIRI Takenobu 埼玉医科大学, 医学部, 教授 (80245802)
• Co-Investigator(Kenkyū-buntansha): FUKUDA Toru 慶應大学, 医学部, 助教 (20301492) ; OHTE Satoshi 埼玉医科大学, 医学部, 助教 (00547979) ; SASANUMA Hiroki 埼玉医科大学, 医学部, 研究員 (30571707) ; YONEYAMA Katsumi 埼玉医科大学, 医学部, 助手 (20571574) ; SHIN Masashi 埼玉医科大学, 医学部, 研究員 (70549261) ; JIMI Eijiro 九州歯科大学, 歯学部, 教授 (40276598)
• Co-Investigator(Renkei-kenkyūsha): AKITA Masumi 埼玉医科大学, 医学部, 教授 (60105905)
• Project Period (FY): 2009 – 2011
• Keywords: 再生 / 蛋白質 / 筋芽細胞 / 細胞・組織 / 骨形成 / 骨芽細胞

Research Abstract

We studied molecular mechanisms of heterotopic bone formation induced by bone morphogenetic protein(BMP) signaling in C2C12 myoblasts. The Smad-dependent pathway plays critical roles for both an induction of osteoblast differentiation and inhibition of myogenesis. The Smad-dependent signaling was suppressed by Zranb2 or DRAGON. In patients with fibrodysplasia ossificans progressiva(FOP), one of BMP receptors, ALK2, was genetically mutated and activated the Smad-dependent signaling regardless of the binding to BMPs.

Research Products

• [Journal Article] Recent topics in fibrodysplasia ossificans progressiva (2012)
  • Author(s): Katagiri T
  • Journal Title: J Oral Biosci Volume: (in press)
  • Peer Reviewed
• [Journal Article] Identification and functional analysis of Zranb2 as a novel Smad-binding protein that suppresses BMP signaling (2011)
  • Author(s): Ohte S, Kokabu S, Iemura S, Sasanuma H, Yoneyama K, Shin M, Suzuki S, Fukuda T, Nakamura Y, Jimi E, Natsume T, and Katagiri T
  • Journal Title: J Cell Biochem Volume: 113 Pages: 808-814
  • 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, Shin M, Sasanuma H, Yoneyama K, Akita M, Ikebuchi K, Jimi E, Maruki Y, Matsuoka M, Nanba 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 and Katagiri T
  • Journal Title: Biochem Biophys Res Commun Volume: 407 Pages: 213-218
  • Peer Reviewed
• [Journal Article] Suppression of BMP-Smad 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, and Katagiri T
  • Journal Title: Mol Endocrinol Volume: 25 Pages: 474-481
  • Peer Reviewed
• [Journal Article] Canonical Wnts and BMPs cooperatively induce osteoblastic differentiation through a GSK3・-dependent but a・-catenin-independent mechanism (2010)
  • Author(s): Fukuda T, Kokabu S, Ohte S, Sasanuma H, Kanomata K, Yoneyama K, Kato H, Akita M, Oda H, and Katagiri T
  • Journal Title: Differentiation Volume: 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, SasanumaH, Yoneyama K, Ueno N, Okazaki Y, Kamijo R, Yoda T, and Katagiri T
  • Journal Title: J Biol Chem Volume: 285 Pages: 15577-15586
  • Peer Reviewed
• [Journal Article] Protein phosphatase magnesium-dependent 1Amediated inhibition of BMP signaling is independent of Smaddephosphorylation (2010)
  • Author(s): Kokabu S, Nojima J, Kanomata K, Ohte S, Yoda T, Fukuda T and Katagiri T
  • Journal Title: J Bone Miner Res Volume: 25 Pages: 653-660
  • Peer Reviewed
• [Journal Article] Heterotopic bone formation induced by bone morphogenetic protein signaling : fibrodysplasia ossificans progressiva (2010)
  • Author(s): Katagiri T
  • Journal Title: J Oral Biosci Volume: 52 Pages: 33-41
  • Peer Reviewed
• [Journal Article] Constitutively activated ALK-2 and increased Smad1/5 cooperatively induce BMP signaling in fibrodysplasia ossificans progressiva (2009)
  • Author(s): Fukuda T, Kohda M, Kanomata K, Nojima J, Nakamura A, Kamizono J, Noguchi Y, Iwakiri K, Kondo T, Kurose J, Endo K, Awakura T, Fukushi J, Nakashima Y, Chiyonobu T, Kawara A, Nishida Y, Wada I, Akita M, Komori T, Nakayama K, Nanba A, Maruki Y, Yoda T, Tomoda H, Yu PB, Shore EM, Kaplan FS, Miyazono K, Matsuoka M, Ikebuchi K, Ohtake A, Oda H, Jimi E, Owan I, Okazaki Y, and Katagiri T
  • Journal Title: J Biol Chem Volume: 284 Pages: 7149-7156
  • Peer Reviewed
• [Journal Article] The fibrodysplasia ossificans progressiva R206H ACVR1 mutation activates BMP-independent chondrogenesis and zebrafish embryo ventralization (2009)
  • Author(s): Shen Q, Little SC, Xu M, Haupt J, Ast C, Katagiri T, Mundlos S, Seemann P, Kaplan FS, Mullins MC and Shore EM
  • Journal Title: J Clin Invest Volume: 119 Pages: 3462-3472
  • Peer Reviewed
• [Journal Article] DRAGON, a GPI-anchored membrane protein, inhibits BMP signaling in C2C12 myoblasts (2009)
  • Author(s): Kanomata K, Kokabu S, Nojima J, Fukuda T and Katagiri T
  • Journal Title: Genes Cells Volume: 14 Pages: 695-702
  • Peer Reviewed
• [Presentation] BMP signaling inhibits myogenesis and induces osteoblastic differentiation in satellite cells during muscle regeneration (2011)
  • Author(s): Katagiri T, et al.
  • Organizer: ASBMR 2011 Annual Meeting
  • Place of Presentation: San Diego, California, U. S. A.
  • Year and Date: 20110916-20
• [Presentation] BMP type II receptors further stimulate constitutively activated mutant ALK2 found in fibrodysplasia ossificans progressiva (2011)
  • Author(s): Ohte S, et al.
  • Organizer: ASBMR 2011 Annual Meeting
  • Place of Presentation: San Diego, California, U. S. A.
  • Year and Date: 20110916-20
• [Presentation] Molecular mechanisms of heterotopic bone formation in skeletal muscle induced by BMP signaling (2011)
  • Author(s): Katagiri T, et al.
  • Organizer: Gordon Research Conference on Myogenesis
  • Place of Presentation: Waterville Valley, New Hampshire, U. S. A.
  • Year and Date: 20110824-0902
• [Presentation] 進行性骨化性線維異形成症(FOP)で同定されたALK2はII型BMP受容体によってさらに活性化される (2011)
  • Author(s): 大手聡, 他
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 20110728-30
• [Presentation] Characterization of mutant forms of ALK2 found in patients with fibrodysplasia ossificans progressiva (2011)
  • Author(s): Katagiri T
  • Organizer: Gordon Research Conference on Myogenesis
  • Place of Presentation: Les Diablerets, Switzerland
  • Year and Date: 20110619-24
• [Presentation] 筋肉が骨になるメカニズム (2011)
  • Author(s): 片桐岳信
  • Organizer: 第9回RCGMフロンティアシンポジウム
  • Place of Presentation: 埼玉県日高市
  • Year and Date: 2011-11-03
• [Presentation] Smadの新規転写抑制因子Zranb2の同定と機能解析 (2011)
  • Author(s): 片桐岳信, 他
  • Organizer: 第53回歯科基礎医学会学術大会演
  • Place of Presentation: 岐阜県岐阜市
  • Year and Date: 2011-10-01
• [Presentation] 新規Smad結合分子Zranb2はBMPシグナル抑制因子である (2011)
  • Author(s): 大手聡, 他
  • Organizer: 第18回BMP研究会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-31
• [Presentation] 筋が骨化する難病進行性骨化性線維異形成症 (2011)
  • Author(s): 片桐岳信
  • Organizer: 第29回日本骨代謝学会学術集会
  • Place of Presentation: 大阪府大阪市
  • Year and Date: 2011-07-29
• [Presentation] Heterotopic bone formation and muscle regeneration (2011)
  • Author(s): Katagiri T
  • Organizer: 32nd Annual Meeting of Japanese Society of Inflammation and Regeneration
  • Place of Presentation: 京都府京都市
  • Year and Date: 2011-06-03
• [Presentation] Identification of Zranb2, a novel R-Smads binding protein, as a suppressor of BMP signaling (2010)
  • Author(s): Ohte S., et al.
  • Organizer: ASBMR(American Society for Bone and Mineral Research) 2010 annual meeting
  • Place of Presentation: カナダ、トロント
  • Year and Date: 20101015-19
• [Presentation] PPM1A and SCP1, Smad phosphatases, inhibit BMP-induced osteoblastic differentiation by different molecular mechanisms (2010)
  • Author(s): Katagiri T, et al.
  • Organizer: 8th International Conference on Bone Morphogenetic Proteins
  • Place of Presentation: ベルギー、ルーベン
  • Year and Date: 20100915-18
• [Presentation] Identification and characterization of a nuclear protein as a co-suppressor of BMP-regulated Smads (2010)
  • Author(s): Ohte S., et al.
  • Organizer: 8th International Conference on Bone Morphogenetic Proteins
  • Place of Presentation: ベルギー、ルーベン
  • Year and Date: 20100915-18
• [Presentation] Potentiation of bone morphogenetic protein activity in the extracellular environment (2010)
  • Author(s): Katagiri T
  • Organizer: Gordon Research Conference on Signal Transduction by Tissue Engineered Extracellular Matrices
  • Place of Presentation: 米国メイン州
  • Year and Date: 20100627-0702
• [Presentation] 骨形成を促すBMP細胞内情報伝達系とその制御機構の解明 (2010)
  • Author(s): 片桐岳信
  • Organizer: 第8回RCGMフロンティア国際シンポジウム
  • Place of Presentation: 埼玉県
  • Year and Date: 2010-11-03
• [Presentation] SmadホスファターゼによるBMP誘導性骨芽細胞分化の抑制機序 (2010)
  • Author(s): 片桐岳信
  • Organizer: 第52回歯科基礎医学会学術大会
  • Place of Presentation: 東京都
  • Year and Date: 2010-09-22
• [Presentation] 筋組織における異所性骨化の機序解明と治療への応用 (2009)
  • Author(s): 片桐岳信
  • Organizer: 第7回RCGMフロンティアシンポジウム
  • Place of Presentation: 埼玉県
  • Year and Date: 2009-11-03
• [Presentation] BMPのSmad依存的シグナルによる筋芽細胞分化の抑制機構 (2009)
  • Author(s): 片桐岳信
  • Organizer: 第64回日本体力医学会大会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-19
• [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): 片桐岳信
  • Organizer: 第51回歯科基礎医学会学術集会・総会
  • Place of Presentation: 新潟
  • Year and Date: 2009-09-10
• [Presentation] Roles of Smad pathways in the conversion of myoblasts to osteoblastic cells by BMPs. (2009)
  • Author(s): Katagiri T
  • Organizer: Gordon Research Conference on Bones & Teeth
  • Place of Presentation: 米国メイン州
  • Year and Date: 2009-07-15
• [Remarks]
  • URL: http://www.saitama-med.ac.jp/genome/Div04_PPhysiol/index.html
• [Patent(Industrial Property Rights)] 骨分化阻害剤およびその製造方法 (2010)
  • Inventor(s): 供田洋,他
  • Industrial Property Rights Holder: 学校法人北里研究所、埼玉医科大学
  • Industrial Property Number: 特願2010-255134
  • Filing Date: 2010-11-15