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L-serine starvation response in osteoclast precursors and its physiological significance in the bone marrow microenvironment

Research Project

Project/Area Number 22791382
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionNara Institute of Science and Technology

Principal Investigator

OGAWA Takuya  奈良先端科学技術大学院大学, バイオサイエンス研究科, 研究員 (30457147)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアミノ酸 / セリン / 細胞・組織 / 発生・分化 / 発現制御 / シグナル伝達 / 骨・軟骨代謝学 / 破骨細胞 / L-セリン / 分化 / アミノ酸飢餓ストレス
Research Abstract

Osteoclasts play central roles in the development and remodeling of bone. In addition to the stimulation by RANKL, serine in the culture medium is necessary for the in vitro differentiation of osteoclasts from their precursors. We conducted a series of experiments to understand the regulatory mechanism of osteoclast differentiation by serine as well as its physiological significance, and found the activation of amino acid starvation response in the precursors by serine deprivation alone, low expression of serine biosynthetic enzymes, and importance of serine supplied by osteoblasts to osteoclasts in the bone marrow microenvironment.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (53 results)

All 2012 2011 2010

All Journal Article (18 results) (of which Peer Reviewed: 16 results) Presentation (35 results)

  • [Journal Article] Siglec-15 regulates the formation of functional osteoclasts in concert with DNAX-activating protein of 12 KDa(DAP12)2012

    • Author(s)
      Ishida-Kitagawa N, 他11名(10番目)
    • Journal Title

      J Biol Chem

      Volume: 287(21) Issue: 21 Pages: 17493-17502

    • DOI

      10.1074/jbc.m111.324194

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Advantages and Potential of Lipid-Membrane- Incorporating Fullerenes Prepared by the Fullerene-Exchange Method2012

    • Author(s)
      Ikeda, M. Mori, K. Kiguchi, K. Yasuhara, J. Kikuchi, K. Nobusawa, M. Akiyama, M. Hashizume, T. Ogawa, T. Takeya
    • Journal Title

      Chem. Asian J

      Volume: Vol.7, No.3 Issue: 3 Pages: 605-613

    • DOI

      10.1002/asia.201100792

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Abi-1-bridged tyrosine phosphorylation of VASP by Abelson kinase impairs association of VASP to focal adhesions and regulates leukemic cell adhesion2012

    • Author(s)
      Maruoka M, 他8名(5番目)
    • Journal Title

      Biochem J

      Volume: 441(3) Issue: 3 Pages: 889-899

    • DOI

      10.1042/bj20110951

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of SAMT family proteins as substrates of MARCH11 in mouse spermatids2012

    • Author(s)
      Yogo, K., Tojima, H., Ohno, J.Y., Ogawa, T., Nakamura, N., ら(計8名)
    • Journal Title

      Histochem.Cell Biol.

      Volume: 137 Issue: 1 Pages: 53-65

    • DOI

      10.1007/s00418-011-0887-y

    • NAID

      120003518501

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The L-Ser analog# 290 promotes bone recovery in OP and RA mice2011

    • Author(s)
      Bahtiar A, 他7名(7番目)
    • Journal Title

      Pharmacol Res

      Volume: 64(3) Issue: 3 Pages: 203-209

    • DOI

      10.1016/j.phrs.2011.05.004

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Purification and identification of lactoperoxidase(LPO) in milk basic proteins(MBP) as an inhibitor of osteoclastogenesis2011

    • Author(s)
      Morita Y, 他6名(7番目)
    • Journal Title

      J Dairy Sci

      Volume: 94(5) Issue: 5 Pages: 2270-2279

    • DOI

      10.3168/jds.2010-4039

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and functional analysis of a new phosphorylation site(Y398) in the SH3 domain of Abi-12011

    • Author(s)
      Sato M, 他8名(7番目)
    • Journal Title

      FEBS Lett

      Volume: 585(6) Issue: 6 Pages: 834-840

    • DOI

      10.1016/j.febslet.2011.02.012

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Acid sphingomyelinase regulates osteoclastogenesis by modulating sphingosine kinases downstream of RANKL signaling2011

    • Author(s)
      Bao X, Ogawa T, 他5名(2番目)
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 405(4) Issue: 4 Pages: 533-537

    • DOI

      10.1016/j.bbrc.2011.01.061

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Purification and identification of Iactoperoxidase (LPO) in milk basic proteins (MBP) as an inhibitor of osteoclastogenesis.2011

    • Author(s)
      Yoshikazu Morita
    • Journal Title

      Journal of Dairy Science

      Volume: (in press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification and functional analysis of a new phosphorylation site (Y398) in the SH3 domain of Abi-1.2011

    • Author(s)
      Mizuho Sato
    • Journal Title

      FEBS Letters

      Volume: 585 Pages: 834-840

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acid sphingomyelinase regulates osteoclastogenesis by modulating sphingosine kinases downstream of RANKL signaling.2011

    • Author(s)
      Xilinqiqige Bao
    • Journal Title

      Biochemical and Biophysical Research Communication

      Volume: 405 Pages: 533-537

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 細胞外L-セリンは破骨細胞前駆細胞のアミノ酸栄養シグナル活性化に必須である2010

    • Author(s)
      小川拓哉, 他7名(1番目)
    • Journal Title

      アミノ酸研究

      Volume: 4(2) Pages: 167-169

    • Related Report
      2011 Final Research Report
  • [Journal Article] Identification and expression analysis of CX45 and CX60 as major connexins in porcine oocytes2010

    • Author(s)
      Nitta,M., Yogo,K., Ohashi,M., Akiyama,M., Kunitomo,Y., Ogawa,T., Ishida-Kitagawa,N., Miyoshi,J., Sato,E., Takeya,T
    • Journal Title

      J.Anim.Sci

      Volume: Vol.88, No. 10 Issue: 10 Pages: 3269-3279

    • DOI

      10.2527/jas.2009-2781

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Photodynamic Activity of Liposomal Photosensitizers via Energy Transfer from Antenna Molecules to[60] Fullerene2010

    • Author(s)
      Ikeda A, 他3名(3番目)
    • Journal Title

      ACS Med Chem Lett

      Volume: 1(3) Issue: 3 Pages: 115-119

    • DOI

      10.1021/ml100021x

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Potential Involvement of Twist2 and Erk in the Regulation of Osteoblastogenesis by HB-EGF-EGFR Signaling2010

    • Author(s)
      Nakamura T, 他7名(6番目)
    • Journal Title

      Cell Structure and Function

      Volume: 35 Issue: 1 Pages: 53-61

    • DOI

      10.1247/csf.10001

    • NAID

      130004053875

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] 細胞外L-セリンは破骨細胞前駆細胞のアミノ酸栄養シグナル活性化に必須である2010

    • Author(s)
      小川拓哉
    • Journal Title

      アミノ酸研究

      Volume: 4 Pages: 167-169

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Identification and expression analysis of connexin-45 and connexin-60 as major connexins in porcine oocytes.2010

    • Author(s)
      Mai Nitta
    • Journal Title

      Journal of Animal Science

      Volume: 88 Pages: 3269-3279

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Photodynamic Activity of Liposomal Photosensitizers via Energy Transfer from Antenna Molecules to [60]Fullerene2010

    • Author(s)
      Atsushi Ikeda
    • Journal Title

      ACS Medicinal Chemistry Letters

      Volume: 1 Pages: 115-119

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Presentation] 破骨細胞における新規DAP12会合膜タンパク質Siglec-15の機能解析2011

    • Author(s)
      北川(石田)教弘
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)
    • Year and Date
      2011-12-14
    • Related Report
      2011 Final Research Report
  • [Presentation] セリン欠乏による遺伝子発現応答にAtf4は関与するか2011

    • Author(s)
      佐矢野智子
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポジオン(名古屋)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Final Research Report
  • [Presentation] セリン欠乏により惹起される細胞内情報伝達系解析2011

    • Author(s)
      川野裕輝
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポジオン(名古屋)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Final Research Report
  • [Presentation] セリン合成酵素Phgdh欠損線維芽細胞に惹起される炎症反応の分子機序2011

    • Author(s)
      濱野桃子
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポジオン(名古屋)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞内セリン充足度と脂質代謝関連遺伝子発現の連動2011

    • Author(s)
      月野真理子
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポジオン(名古屋)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Final Research Report
  • [Presentation] セリン欠乏による遺伝子発現応答にAtf4は関与するか?2011

    • Author(s)
      佐矢野智子, 和田晃, 濱野桃子, 鵜殿美弥子, 片倉喜範, 小川拓哉, 加藤久典, 古屋茂樹
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポシオン(名古屋)(一般演題)(ポスター発表)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] セリン欠乏により惹起される細胞内情報伝達系解析2011

    • Author(s)
      川野裕輝, 佐矢野智子, 有本八潮, 小川拓哉, 平林義雄, 古屋茂樹
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポシオン(名古屋)(一般演題)(ポスター発表)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] セリン合成酵素Phgdh欠損線維芽細胞に惹起される炎症反応の分子機序2011

    • Author(s)
      濱野桃子, 佐矢野智子, 小川拓哉, 加藤久典, 古屋茂樹
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポシオン(名古屋)(一般演題)(ポスター発表)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 細胞内セリン充足度と脂質代謝関連遺伝子発現の連動2011

    • Author(s)
      月野真理子, 草田航, 佐矢野智子, 濱野桃子, 小川拓哉, 加藤久典, 平林義雄, 古屋茂樹
    • Organizer
      日本アミノ酸学会第5回学術大会
    • Place of Presentation
      名古屋大学シンポシオン(名古屋)(一般演題)(ポスター発表)
    • Year and Date
      2011-11-04
    • Related Report
      2011 Annual Research Report
  • [Presentation] 破骨細胞分化におけるセリン要求性とセリン供給細胞としての骨芽細胞の検討2011

    • Author(s)
      小川拓哉
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2011-07-30
    • Related Report
      2011 Final Research Report
  • [Presentation] 破骨細胞分化におけるセリン要求性とセリン供給細胞としての骨芽細胞の検討2011

    • Author(s)
      小川拓哉, 北川(石田)教弘
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)(一般演題)(ポスター発表)
    • Year and Date
      2011-07-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] 破骨細胞における新規DAP12会合膜タンパク質の機能解析2011

    • Author(s)
      北川(石田)教弘
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)
    • Year and Date
      2011-07-29
    • Related Report
      2011 Final Research Report
  • [Presentation] 破骨細胞における新規DAP12会合膜タンパク質の機能解析2011

    • Author(s)
      北川(石田)教弘, 小川拓哉
    • Organizer
      第29回日本骨代謝学会学術集会
    • Place of Presentation
      大阪国際会議場(大阪)(一般演題)(ポスター発表)
    • Year and Date
      2011-07-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] セリン欠乏に応答する遺伝子の発現誘導機序2011

    • Author(s)
      佐矢野智子
    • Organizer
      第65回日本栄養・食料学会大会
    • Place of Presentation
      お茶の水女子大学(東京)
    • Year and Date
      2011-05-15
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞外セリンを介した新たな破骨細胞分化制御機構2011

    • Author(s)
      小川拓哉
    • Organizer
      第65回日本栄養・食料学会大会
    • Place of Presentation
      お茶の水女子大学(東京)
    • Year and Date
      2011-05-14
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞外セリンを介した新たな破骨細胞分化制御機構2011

    • Author(s)
      小川拓哉
    • Organizer
      第65回日本栄養・食料学会大会
    • Place of Presentation
      お茶の水女子大学(東京)(シンポジウム)(口頭発表)
    • Year and Date
      2011-05-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] 破骨細胞における新規DAP12会合膜タンパク質Siglec-15の機能解析2011

    • Author(s)
      北川(石田)教弘, 田中國太郎, Bao Xilinqiqige, 木村貴徳, 三浦格, 北岡良基, 小川拓哉
    • Organizer
      第34回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(横浜)(一般演題)(口頭・ポスター発表)
    • Related Report
      2011 Annual Research Report
  • [Presentation] マウス前駆破骨細胞のセリン取り込みに関与するアミノ酸トランスポーターの解析2010

    • Author(s)
      岸田耕一
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
    • Place of Presentation
      神戸国際展示場(神戸)
    • Year and Date
      2010-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞外セリンによるマウス前駆破骨細胞のアミノ酸シグナル応答経路の制御2010

    • Author(s)
      藤井直樹
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
    • Place of Presentation
      神戸国際展示場(神戸)
    • Year and Date
      2010-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] 骨吸収の異常亢進による骨代謝疾患に対するセリンアナログ# 290の投与効果の検討2010

    • Author(s)
      桂準平
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会合同大会)
    • Place of Presentation
      神戸国際展示場(神戸)
    • Year and Date
      2010-12-09
    • Related Report
      2011 Final Research Report
  • [Presentation] マウス前駆破骨細胞のセリン取り込みに関与するアミノ酸トランスポーターの解析2010

    • Author(s)
      岸田耕一
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 細胞外セリンによるマウス前駆破骨細胞のアミノ酸シグナル応答経路の制御2010

    • Author(s)
      藤井直樹
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] 骨吸収の異常亢進による骨代謝疾患に対するセリンアナログ#290の投与効果の検討2010

    • Author(s)
      桂準平
    • Organizer
      BMB2010(第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会)
    • Place of Presentation
      兵庫県神戸市
    • Year and Date
      2010-12-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] Identification and Functional Analysis of a Novel Regulator of Actin-ring Formation in Osteoclast2010

    • Author(s)
      Ishida-Kitagawa N
    • Organizer
      32nd Annual Meeting of The American Society for Bone and Mineral Research
    • Place of Presentation
      Metro Toronto Convention Centre(Toronto)
    • Year and Date
      2010-10-18
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification and Functional Analysis of a Novel Regulator of Actin-ring Formation in Osteoclast.2010

    • Author(s)
      Norihiro Ishida-Kitagawa
    • Organizer
      32nd Annual Meeting of The American Society for Bone and Mineral Research
    • Place of Presentation
      Toronto, Ontario, Canada
    • Year and Date
      2010-10-18
    • Related Report
      2010 Annual Research Report
  • [Presentation] Extracellular L-Serine Regulates Intracellular Amino Acid Levels and mTORC1 Activation in Mouse Osteoclast Precursors2010

    • Author(s)
      Ogawa T
    • Organizer
      32nd Annual Meeting of The American Society for Bone and Mineral Research
    • Place of Presentation
      Metro Toronto Convention Centre(Toronto)
    • Year and Date
      2010-10-17
    • Related Report
      2011 Final Research Report
  • [Presentation] Extracellular L-Serine Regulates Intracellular Amino Acid Levels and mTORC1 Activation in Mouse Osteoclast Precursors.2010

    • Author(s)
      Takuya Ogawa
    • Organizer
      32nd Annual Meeting of The American Society for Bone and Mineral Research
    • Place of Presentation
      Toronto, Ontario, Canada
    • Year and Date
      2010-10-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 細胞外L-セリンは破骨細胞前駆細胞のアミノ酸栄養シグナル活性化に必須である2010

    • Author(s)
      小川拓哉
    • Organizer
      日本アミノ酸学会第4回学術大会
    • Place of Presentation
      ホテルサンシャイン鬼怒川(日光)
    • Year and Date
      2010-09-17
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞外L-セリンは破骨細胞前駆細胞のアミノ酸栄養シグナル活性化に必須である2010

    • Author(s)
      小川拓哉
    • Organizer
      日本アミノ酸学会第4回学術大会
    • Place of Presentation
      栃木県日光市
    • Year and Date
      2010-09-17
    • Related Report
      2010 Annual Research Report
  • [Presentation] 細胞外L-セリンはアミノ酸栄養シグナルを介して破骨細胞分化を制御する2010

    • Author(s)
      小川拓哉
    • Organizer
      第28回日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2010-07-22
    • Related Report
      2011 Final Research Report
  • [Presentation] 細胞外L-セリンはアミノ酸栄養シグナルを介して破骨細胞分化を制御する2010

    • Author(s)
      小川拓哉
    • Organizer
      第28回日本骨代謝学会学術集会
    • Place of Presentation
      東京都新宿区
    • Year and Date
      2010-07-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] 破骨細胞における膜タンパク質の網羅的解析と新規アクチン細胞骨格制御因子の同定2010

    • Author(s)
      北川(石田)教弘
    • Organizer
      第28回日本骨代謝学会学術集会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2010-07-21
    • Related Report
      2011 Final Research Report
  • [Presentation] 破骨細胞における膜タンパク質の網羅的解析と新規アクチン細胞骨格制御因子の同定2010

    • Author(s)
      北川(石田)教弘
    • Organizer
      第28回日本骨代謝学会学術集会
    • Place of Presentation
      東京都新宿区
    • Year and Date
      2010-07-21
    • Related Report
      2010 Annual Research Report
  • [Presentation] Isolation of L-Ser analogs as novel inhibitors of osteoclastogenesis and bone turnover with distinct functional mechanism2010

    • Author(s)
      Takeya T
    • Organizer
      IOF World Congress on Osteoporosis & 10th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis
    • Place of Presentation
      Fortezza da Basso(Florence)
    • Year and Date
      2010-05-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Isolation of L-Ser analogs as novel inhibitors of osteoclastogenesis and bone turnover with distinct functional mechanism.2010

    • Author(s)
      Tatsuo Takeya
    • Organizer
      IOF World Congress on Osteoporosis & 10th European Congress on Clinical and Economic Aspects of Osteoporosis and Osteoarthritis
    • Place of Presentation
      Florence, Italy
    • Year and Date
      2010-05-07
    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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