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Research of bone and cartilage regulation by NF-kB signal for innovative targeted therapy.

Research Project

Project/Area Number 21390415
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

ITO Hideya  東京大学, 医学部附属病院, 助教 (30436464)

Co-Investigator(Kenkyū-buntansha) ITO Hideya  東京大学, 医学部附属病院, 助教 (30436464)
OGATA Naoshi  東京大学, 医学部附属病院, 講師 (10361495)
CHIKUDA Hirotaka  東京大学, 医学部附属病院, 助教 (30345219)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2011: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2010: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000)
Fiscal Year 2009: ¥7,540,000 (Direct Cost: ¥5,800,000、Indirect Cost: ¥1,740,000)
Keywords骨・軟骨代謝学 / NF-kB / 骨軟骨代謝学 / 再生医学 / 発生・分化 / NFκB
Research Abstract

Among transcription factors whose binding motifs were identified in the highly-conserved regions between human and mouse SOX9 promoters, a nuclear factor kappa B(NF-kB) member RelA strongly activated the promoter activity. RelA and SOX9 were co-localized in the limb cartilage. Deletion, mutagenesis, and tandem-repeat analyses identified the core region responsive to RelA at the NF-kB binding motif to be around-250 bp of the human SOX9 promoter, and this was confirmed to show specific binding to RelA. RelA induced the chondrogenic differentiation parameters in HeLa and ATDC5 cells. In conclusion, we have identified RelA as a transcriptional factor for SOX9 induction and chondrogenic differentiation via binding to an NF-kB binding motif in the SOX9 promoter.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (51 results)

All 2012 2011 2010 2009 Other

All Journal Article (36 results) (of which Peer Reviewed: 36 results) Presentation (11 results) Remarks (4 results)

  • [Journal Article] Lack of a chondroprotective effect of cyclooxygenase 2 inhibition in a surgically induced model of osteoarthritis in mice2012

    • Author(s)
      Fukai A, et al
    • Journal Title

      Arthritis Rheum

      Volume: 64(1) Pages: 198-203

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] C/EBPβand RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2αas the inducer in chondrocytes2012

    • Author(s)
      Hirata M, et al
    • Journal Title

      Hum Mol Genet

      Volume: 21(5) Pages: 1111-23

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biomimetic hydration lubrication with various polyelectrolyte layers on cross-linked polyethylene orthopedic bearing materials2012

    • Author(s)
      Kyomoto M, Ito H, et al.
    • Journal Title

      Biomaterials

      Volume: (E-pub)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mortality and morbidity in dialysis-dependent patients undergoing spinal surgery : analysis of a national administrative database in Japan2012

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

      J Bone Joint Surg Am

      Volume: 94 Pages: 433-8

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The normative score and the cut-off value of the Oswestry Disability Index (ODI)2012

    • Author(s)
      Tonosu J, Chikuda H, et al.
    • Journal Title

      Eur Spine J

      Volume: (E-pub)

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] G alpha(q) signal in osteoblasts is inhibitory to the osteoanabolic action of parathyroid hormone2011

    • Author(s)
      Ogata N, et al
    • Journal Title

      J Biol Chem

      Volume: 286(15) Pages: 13733-40

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] G alpha(q) signal in osteoblasts is inhibitory to the osteoanabolic action of parathyroid hormone2011

    • Author(s)
      Ogata N, et al.
    • Journal Title

      J Biol Chem

      Volume: 286 Pages: 13733-40

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ossification of the posterior atlantoaxial membrane associated with anos odontoideum : a case report2011

    • Author(s)
      Ohya J, Chikuda H, et al.
    • Journal Title

      J Orthop Surg

      Volume: 19 Pages: 392-4

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Use of Doppler ultrasonography to detect an elusive communication of a spinal extradural arachnoid cyst2011

    • Author(s)
      Kanetaka M, Chikuda H, et al.
    • Journal Title

      J Clin Neurosci

      Volume: 18 Pages: 863-4

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute cervical spinal cord injury complicated by preexisting ossification of the posterior longitudinal ligament : a multicenter study2011

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

      Spine

      Volume: 36 Pages: 1453-8

    • NAID

      10030716761

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The G&alpha ; q signal in osteoblasts is inhibitory to the osteoanabolic action of PTH.2011

    • Author(s)
      Ogata N, et al.
    • Journal Title

      J Biol Chem

      Volume: (Epub)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Neurological complications of cervical laminoplasty for patients with ossification of the posterior longitudinal ligament-A multi-instituitional retrospective study-2011

    • Author(s)
      Seichi A, Chikuda H, et al.
    • Journal Title

      Spine

      Volume: (Epub)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Is a Right Pedicle Screw Always Away from the Aorta in Scoliosis?2011

    • Author(s)
      Takeshita K, Chikuda H, et al.
    • Journal Title

      Spine

      Volume: (Epub)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Acute Cervical Spinal Cord Injury Complicated by Pre-existing Ossification of the Posterior Longitudinal Ligament : A Multi-center Study.2011

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

      Spine

      Volume: (Epub)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Postsurgical spinal magnetic resonance imaging with iterative decomposition of water and fat with echo asymmetry and least-squares estimation.2011

    • Author(s)
      Murakami M, Chikuda H, et al.
    • Journal Title

      J Comput Assist Tomogr

      Volume: 35 Pages: 16-20

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt1 in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditions2010

    • Author(s)
      Fukai A, et al
    • Journal Title

      Arthritis Rheum

      Volume: 62(3) Pages: 826-36

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development2010

    • Author(s)
      Saito T, et al
    • Journal Title

      Nat Med

      Volume: 16(6) Pages: 678-86

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms underlying catabolic and anabolic functions of parathyroid hormone on bone by combination of culture systems of mouse cells2010

    • Author(s)
      Shinoda Y, et al
    • Journal Title

      J Cell Biochem

      Volume: 109(4) Pages: 755-63

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Akt1 in murine chondrocytes controls cartilage calcification during endochondral ossification under physiologic and pathologic conditions.2010

    • Author(s)
      Fukai A, Ogata N, et al.
    • Journal Title

      Arthritis Rheum

      Volume: 62 Pages: 826-836

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antiapoptotic molecule Bcl-2 is essential for the anabolic activity of parathyroid hormone in bone.2010

    • Author(s)
      Nagase Y, Ogata N, et al.
    • Journal Title

      Ann N Y Acad Sci

      Volume: 1192 Pages: 330-337

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Aorta movement in patients with scoliosis after posterior surgery.2010

    • Author(s)
      Takeshita K, Chikuda H, et al.
    • Journal Title

      Spine

      Volume: 35

    • NAID

      10028263694

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intraoperative ultrasonographic evaluation of posterior decompression via laminoplasty in patients with cervical ossification of the posterior longitudinal ligament : correlation with 2-year follow-up results.2010

    • Author(s)
      Seichi A, Chikuda H, et al.
    • Journal Title

      J Neurosurg Spine

      Volume: 13 Pages: 47-51

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Long-term follow-up of the progression of ossification of the posterior longitudinal ligament.2010

    • Author(s)
      Murakami M, Chikuda H, et al.
    • Journal Title

      J Neurosurg Spine

      Volume: 12 Pages: 577-579

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation between pyramidal signs and the severity of cervical myelopathy.2010

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

      Eur Spine J

      Volume: 19 Pages: 1684-1689

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New parameters to represent the position of the aorta relative to the spine for pedicle screw placement.2010

    • Author(s)
      Takeshita K, Chikuda H, et al.
    • Journal Title

      Eur Spine J

      Volume: 19 Pages: 815-820

    • NAID

      10027068883

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation between pyramidal signs and the severity of cervical myelopathy.2010

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

      Eur Spine J. (E-pub)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Akt1 in murine chondrocytes sontrols cartilage calcification during endochondral ossification under physiologic and pathologic conditions.2010

    • Author(s)
      Fukai A, Ogata N, et al.
    • Journal Title

      Arthritis Rheum 62

      Pages: 826-36

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New parameters to represent the position of the aorta relative to the spine for pedicle screw placement2010

    • Author(s)
      Takeshita K, Chikuda H, et al.
    • Journal Title

      Eur Spine J (E-pub)

    • NAID

      10027068883

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Transcriptional induction of SOX9 by NF-kappaB family member RelA in chondrogenic cells2009

    • Author(s)
      Ushita M, et al
    • Journal Title

      Osteoarthritis Cartilage

      Volume: 17(8) Pages: 1065-75

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Screening of chondrogenic factors with a real-time fluorescence-monitoring cell line ATDC5-C2ER : identification of sorting nexin 19 as a novel factor2009

    • Author(s)
      Kan A, et al
    • Journal Title

      Arthritis Rheum

      Volume: 60(11) Pages: 3314-23

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Wear resistance of artificial hip joints with poly(2-methacryloyloxyethyl phosphorylcholine)grafted polyethylene : Comparisons with the effect of polyethylene cross-linking and ceramic femoral heads.2009

    • Author(s)
      Moro T, Ito H, et al
    • Journal Title

      Biomaterials 30

      Pages: 2995-3001

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms underlying catabolic and anabolic functions of PTH2009

    • Author(s)
      Shinoda Y, Ogata N, et.al.
    • Journal Title

      Jounal of Cellular Biochemistry 109

      Pages: 755-763

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Screening of chondrogenic factors with a real-time fluorescence-monitoring cell line ATDC5-C2ER : identification of sorting nexin 19 as a novel factor.2009

    • Author(s)
      Kan A, Ogata N, et al.
    • Journal Title

      Arthritis Rheum 60

      Pages: 3314-23

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modified fenestration with restorative spinoplasty for lumbar spinal stenosis.2009

    • Author(s)
      Matsudaira K, Chikuda H, et al.
    • Journal Title

      J Neurosurg Spine 10

      Pages: 587-94

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sleep apnea in rheumatoid arthritis patients with occipitoce rvical lesions : the prevalence and associated radiographic features2009

    • Author(s)
      Shoda N, Chikuda H, et al.
    • Journal Title

      Eur Spine J. 18

      Pages: 905-10

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Diameter, length, and direction of pedicle screws for scoliotic spine : analysis by multiplanar reconstruction of computed tomography.2009

    • Author(s)
      Takeshita K, Chikuda H, et al.
    • Journal Title

      Spine 34

      Pages: 798-803

    • NAID

      10027240750

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] Functional Redundancy of GSK-3αand GSK-3βto Control Chondrocyte Differentiation through Phosphorylation of RelA/NF-κB p652011

    • Author(s)
      Itoh S, et al
    • Organizer
      The American Society for Bone and Mineral Research(ASBMR)
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-09-19
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional Redundancy of GSK-3α and GSK-3β to Control Chondrocyte Differentiation through Phosphorylation of RelA/NF-κB p652011

    • Author(s)
      Itoh S, et al.
    • Organizer
      The American Society for Bone and Mineral Research(ASBMR)
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2011-09-19
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional Redundancy of GSK-3αand GSK-3βto Control Chondrocyte Differentiation through Phosphorylation of RelA/NF-κB p652011

    • Author(s)
      Itoh S, et al
    • Organizer
      Osteoarthritis Research Society International(OARSI)
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-09-16
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional Redundancy of GSK-3α and GSK-3β to Control Chondrocyte Differentiation through Phosphorylation of RelA/NF-κB p652011

    • Author(s)
      Itoh S, et al.
    • Organizer
      Osteoarthritis Research Society International(OARSI)
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2011-09-16
    • Related Report
      2011 Annual Research Report
  • [Presentation] Transcriptional induction of ADAMTS5 by NF-κΒfamily member RelA/p65 in chondrocytes during osteoarthritis development2011

    • Author(s)
      Kobayashi H, et al
    • Organizer
      International Osteoporosis Federation/Australian and New Zealand Bone & Mineral Society
    • Place of Presentation
      Gold coast(AUS)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Final Research Report
  • [Presentation] Transcriptional induction of ADAMTS5 by NF-κB family member RelA/p65 in chondrocytes during osteoarthritis development2011

    • Author(s)
      Kobayashi H, et al.
    • Organizer
      International Osteoporosis Federation/Australian and New Zealand Bone & Mineral Society
    • Place of Presentation
      Gold coast (AUS)
    • Year and Date
      2011-09-07
    • Related Report
      2011 Annual Research Report
  • [Presentation] Functional Redundancy of GSK-3αand GSK-3βto Control Chondrocyte Differentiation through Phosphorylation of RelA/NF-κB p652011

    • Author(s)
      Itoh S, et al
    • Organizer
      International Osteoporosis Federation/Australian and New Zealand Bone & Mineral Society
    • Place of Presentation
      Gold coast(AUS)
    • Year and Date
      2011-09-05
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional Redundancy of GSK-3α and GSK-3β to Control Chondrocyte Differentiation through Phosphorylation of RelA/NF-κB p652011

    • Author(s)
      Itoh S, et al.
    • Organizer
      International Osteoporosis Federation/Australian and New Zealand Bone & Mineral Society
    • Place of Presentation
      Gold coast (AUS)
    • Year and Date
      2011-09-05
    • Related Report
      2011 Annual Research Report
  • [Presentation] HIF2A/NF-kB signal in chondrocytes controls extensive steps of osteoarthritis development in mice and human2010

    • Author(s)
      Fukai A, et al
    • Organizer
      2010 World Congress on Osteoarthritis
    • Place of Presentation
      Brussels, Belgium
    • Year and Date
      2010-09-23
    • Related Report
      2011 Final Research Report
  • [Presentation] HIF2A/NF-kB signal in chondrocytes controls extensive steps of osteoart hritis development in mice and human.2010

    • Author(s)
      Fukai A, Ogata N, et al.
    • Organizer
      2010 World Congress on Osteoarthritis
    • Place of Presentation
      Brussels, Belgium
    • Year and Date
      2010-09-23
    • Related Report
      2010 Annual Research Report
  • [Presentation] Regulator of G protein signaling(RGS)-2 enhances bone anabolic action of PTH through inhibition of Gαq/PKC pathway in osteoblasts.2009

    • Author(s)
      Ogata N, et al.
    • Organizer
      31th annual meeting of the American Society for Bone and Mineral Research
    • Place of Presentation
      Denver, CO, USA
    • Related Report
      2009 Annual Research Report
  • [Remarks]

    • URL

      http://www.u-tokyo-ortho.jp/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/ortho/

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/ortho/

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.h.u-tokyo.ac.jp/ortho/

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2009-04-01   Modified: 2016-04-21  

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