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Mechanism of maintainace of articular chondrocyte by NF-kB signaling.

Research Project

Project/Area Number 15K10460
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

Kobayashi Hiroshi  東京大学, 医学部附属病院, 助教 (20407951)

Co-Investigator(Kenkyū-buntansha) 澤田 良子  東京大学, 医学部附属病院, 病院診療医 (30648308)
矢野 文子  東京大学, 医学部附属病院, 特任講師 (80529040)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsNF-kBシグナル / 変形性関節症 / NF-κB シグナル
Outline of Final Research Achievements

We examined the function of NF-kB signalling in articular chondrocyte both in vitro and in vivo to realize the prevention of degeneration and regeneration of articular chondrocyte . We analyze in vivo functions of Rela in embryonic limbs and adult articular cartilage, and find that Rela protects chondrocytes from apoptosis through induction of anti-apoptotic genes. In articular cartilage, homozygous knockout of Rela at 7 weeks leads to marked acceleration of osteoarthritis through enhanced chondrocyte apoptosis, whereas heterozygous knockout of Rela results in suppression of osteoarthritis development through inhibition of catabolic gene expression. Haploinsufficiency or a low dose of an IKK inhibitor suppresses catabolic gene expression, but does not alter anti-apoptotic gene expression. The biphasic regulation of chondrocytes by Rela contributes to understanding the pathophysiology of osteoarthritis.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (1 results)

All 2016

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results)

  • [Journal Article] Biphasic regulation of chondrocytes by Rela through induction of anti-apoptotic and catabolic target genes.2016

    • Author(s)
      Kobayashi H, Chang SH, Mori D, Itoh S, Hirata M, Hosaka Y, Taniguchi Y, Okada K, Mori Y, Yano F, Chung UI, Akiyama H, Kawaguchi H, Tanaka S, Saito T.
    • Journal Title

      Nat Commun.

      Volume: 10

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access

URL: 

Published: 2015-04-16   Modified: 2019-03-29  

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