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老化抑制遺伝子Klothoの発現調節に関する萌芽的研究

Research Project

Project/Area Number 18659436
Research Category

Grant-in-Aid for Exploratory Research

Allocation TypeSingle-year Grants
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

川口 浩  The University of Tokyo, 医学部・附属病院, 准教授 (40282660)

Co-Investigator(Kenkyū-buntansha) 中山 修一  東京大学, 医学部・附属病院, 医員 (80401066)
原 慶宏  東京大学, 医学部・附属病院, 助教 (00422296)
村上 元昭  東京大学, 医学部附属病院, 医員 (50396751)
Project Period (FY) 2006 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2008: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2007: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Keywords老化 / klotho / 転写制御 / プロモータ
Research Abstract

1)発現クロー二ング、サウズウエスタンスクリーニングによるklotho上流分子の探索 昨年までのルシフェラーゼアッセイを用いた検討で、klotho遺伝子プロモーター応答領域は転写開始点から-98bp〜-68bpおよび-53bpから〜15bpに存在することを突き止めた。本年度は、培養液中の血清に有無によって両シスエレメントに結合する分子め存在をgel-shift assayで確認した。その結果、-98bp〜-68bpへの特異的な結合がprobe mutagenesis、非標識probeによる競合阻害によって証明された。一方、-53bpから〜15bpの領域は発現のベースラインの維持に必要と推測された。更にinvivoでの結合もクロマチン免疫沈降法(ChlP)で確認された。しかしながら、両領域には既知の転写因子結合モチーフは存在せず、転写因子の特定に至ることは出来なかった。
2)リン、Vit.Dによるklotho転写制御の検討 リンおよびVit.Dの投与によってklotho mRNA量が増加することをreal-time PCRで確認した。上記で同定したklothoプロモータコンストラクトを用いて、リン、Vit.Dの応答エレメントの同定を試みたが、結合部位および下流分子の同定にはいたらなかった。また、gel-shift assayおよびChlPによっても、リン、Vit.Dによって結合の増加する分子を特定することは出来なかった。

Report

(3 results)
  • 2008 Annual Research Report
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (34 results)

All 2008 2007 2006 Other

All Journal Article (30 results) (of which Peer Reviewed: 12 results) Presentation (1 results) Book (2 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Analysis of the Runx2 promoter in osseous and non-osseous cells and identificationl of HIF2A as a potent transcriptional activator.2008

    • Author(s)
      Hiroyuki Tamiya, et al.
    • Journal Title

      Gene 416

      Pages: 53-60

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity.2008

    • Author(s)
      Shinsuke Ohba, et al.
    • Journal Title

      Dev Cell 14

      Pages: 689-699

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of GSK-3β by cGMP-dependent protein kinase II promotes hypertrophic differentiation of murine chondrocytes.2008

    • Author(s)
      Yosuke Kawasaki, et al
    • Journal Title

      J Clin Invest 118

      Pages: 2506-2515

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effect of 2-methacryloyloxyethyl phosphorylcholine concentration on photo-induced graft polymerizatlion of polyethylene in reducing the wear of orthopaedic bearing surface.2008

    • Author(s)
      Masayuki Kyomoto, et al.
    • Journal Title

      J Biomed Mater Res A 86

      Pages: 439-447

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The distinct role of the Runx proteins in chondrocyte differentiation and intervertebral disc degeneration: Findings in murine models and in human disease.2008

    • Author(s)
      Shingo Sato, et al.
    • Journal Title

      Arthitis Rheum 58

      Pages: 2764-2775

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kruppel-like factor 5 causes cartilage degradation through transactivation of matrix metalloproteinase 9.2008

    • Author(s)
      Yusuke Shinoda, et al.
    • Journal Title

      J Biol Chem 283

      Pages: 24682-64689

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pivotal role of Bcl-2 family proteins in the regulation of chondrocyte apoptosis.2008

    • Author(s)
      Yasushi Oshima, et al.
    • Journal Title

      J Biol Chem 283

      Pages: 26499-26508

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fully automatic quantification of knee osteoarthritis severity on plain radiographs.2008

    • Author(s)
      Hiroyuki Oka, et al.
    • Journal Title

      Osteoarthritis Cartilage 16

      Pages: 1300-1306

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dnm3os, a non-coding RNA, is required for normal growth and skeletal development in mice.2008

    • Author(s)
      Tokumitu Watanabe, et al.
    • Journal Title

      Dev Dynam 237

      Pages: 3738-3748

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of the core element responsive to runt-related transcription factor 2 in the promoter of human type x collagen gene.2008

    • Author(s)
      Akiro Higashikawa, et al.
    • Journal Title

      Arthitis Rheum 60

      Pages: 166-178

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiographic analysis of the cervical spine in patients with retro-odontoid pseudotumors.2008

    • Author(s)
      Hirotaka Chikuda, et al.
    • Journal Title

      Spine 34

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] C/EBPβ promotes transition from proliferation to hypertrophic differentiation of chondrocytes through transactivation of p57^<Kip2>.2008

    • Author(s)
      Makoto Hirata, et al.
    • Journal Title

      PloS ONE 4

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Impaired bone fracture healing in matrix metalloproteinase-13 deficient mice.2007

    • Author(s)
      Naoto Kosaki, et al.
    • Journal Title

      Biochem Biophys Res Commun 354

      Pages: 846-851

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Local application of recombinant human fibroblast growth factor-2 on bone repair : a dose-escalation prospective trial on patients with osteotomy.2007

    • Author(s)
      Hiroshi Kawaguchi, et al.
    • Journal Title

      J Orthop Res 25

      Pages: 480-487

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Molecular backgrounds of age-related osteoporosis from mouse genetics approaches.2006

    • Author(s)
      Hiroshi Kawaguchi, et al.
    • Journal Title

      Rev Endocr Metab Disord 7

      Pages: 17-22

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Suppression of adjuvant-induced arthritic bone destruction by cyclooxygenase-2 selective agents with and without inhibitory potency against carbonic anhydrase II.2006

    • Author(s)
      Mika Katagiri, et al.
    • Journal Title

      J Bone Miner Res 21

      Pages: 219-227

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Carminerin contributes to chondrocyte calcification during endochondral ossification.2006

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

      Nature Med 12

      Pages: 665-670

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Contribution of runt-related transcription factor 2 to the pathogenesis of osteoarthritis in mice after induction of knee joint instability. Runx2 contributes to pathogenesis of osteoarthritis in mice after induction of knee joint instability.2006

    • Author(s)
      Satoru Kamekura, et al.
    • Journal Title

      Arthritis Rheum 54

      Pages: 2462-2470

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Physiological role of bone morphogenetic proteins in osteogenesis.2006

    • Author(s)
      Fumitaka Kugimiya, et al.
    • Journal Title

      J Bone Miner Metab 24

      Pages: 95-99

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Risk factors for knee osteoarthritis in Japanese men : a case-control study.2006

    • Author(s)
      Noriko Yoshimura, et al.
    • Journal Title

      Mod Rheumatol 16

      Pages: 24-29

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cartilage tissue engineering using human auricular chondrocytes embedded in different hydrogel materials.2006

    • Author(s)
      Hisayo Yamaoka, et al.
    • Journal Title

      J Biomed Mater Res A 78

      Pages: 1-11

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Decreased activities of daily living and associations with bone loss among aged residents in a rural Japanese community : the Miyama Study.2006

    • Author(s)
      Hiroyuki Oka, et al.
    • Journal Title

      J Bone Miner Metab 24

      Pages: 307-313

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Regulation of bone formation by adiponectin through autocrine/paracrine and endocrine pathways.2006

    • Author(s)
      Yusuke Shinoda, et al.
    • Journal Title

      J Cell Biochem 99

      Pages: 196-208

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Distinct association of gene polymorphisms of estrogen receptor and vitamin D receptor with lumbar spondylosis in postmenopausal women.2006

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

      Eur Spine J 15

      Pages: 1521-1528

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Grafting of biocompatible polymer for longevity of artificial hip joints.2006

    • Author(s)
      Toru Moro, et al.
    • Journal Title

      Clin Orthop Rel Res 453

      Pages: 58-63

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Tailor-made tricalcium phosphate bone implant directly fabricated by a three-dimensional ink-jet printer.2006

    • Author(s)
      Kazuyo Igawa, et al.
    • Journal Title

      J Artif Organs 9

      Pages: 234-240

    • Related Report
      2006 Annual Research Report
  • [Journal Article] 骨・軟骨再生促進因子2006

    • Author(s)
      川口浩
    • Journal Title

      分子リウマチ 3-2

      Pages: 107-115

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification and characterization of the human SOX6 Promoter.

    • Author(s)
      Toshiyuki Ikeda, et al.
    • Journal Title

      Biochem Biophys Res Commun (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of a potent combination of osteogenic genes for bone regeneration using embryonic stem (ES) cell-based sensor.

    • Author(s)
      Shinsuke Ohba, et al.
    • Journal Title

      FASEB J (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] S100A1 and B, transcriptional targets of SOX trio, inhibit terminal differentiation of chondrocytes.

    • Author(s)
      Taku Saito, et al.
    • Journal Title

      EMBO Rep (印刷中)

    • Related Report
      2006 Annual Research Report
  • [Presentation] Transcriptional regulation of osteoarthritis progression2008

    • Author(s)
      Hiroshi Kawaguchi
    • Organizer
      The 13th Congress of the Asia Pacific League of Associatjons for Rheumatology (APLAR 2008).
    • Place of Presentation
      Yokohama
    • Related Report
      2008 Annual Research Report
  • [Book] 運動器リハビリテーションクルズス2008

    • Author(s)
      川口浩
    • Total Pages
      443
    • Publisher
      南江堂
    • Related Report
      2008 Annual Research Report
  • [Book] OPLL - Ossification of the Posterior Longitudinal Ligament - 2nd Edition (edited by K. Yonenobu, T. Nakamura, and Y. Toyama)2006

    • Author(s)
      Hiroshi Kawaguchi, et al.
    • Total Pages
      1023
    • Publisher
      Springer-Verlag Tokyo
    • Related Report
      2006 Annual Research Report
  • [Patent(Industrial Property Rights)] 低摩耗性摺動部材及びそれを用いた人工関節2006

    • Inventor(s)
      京本政之, 二塚健, 石原一彦, 金野智浩, 中村耕三, 高取吉雄, 川口浩, 茂呂徹, 橋本雅美
    • Industrial Property Rights Holder
      京本政之, 二塚健, 石原一彦, 金野智浩, 中村耕三, 高取吉雄, 川口浩, 茂呂徹, 橋本雅美
    • Filing Date
      2006-12-15
    • Related Report
      2006 Annual Research Report

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

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