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The effect of dysregulated circadian rhythm gene expression on articular cartilage homeostasis

Research Project

Project/Area Number 16K20035
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Orthopaedic surgery
Research InstitutionChiba University

Principal Investigator

Akagi Ryuichiro  千葉大学, 大学院医学研究院, 助教 (10638315)

Research Collaborator LOTZ K. martin  
ENOMOTO takahiro  
SATO yusuke  
NAKAGAWA ryosuke  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords軟骨細胞 / 変形性膝関節症 / 概日リズム / NR1D1 / BMAL1 / シグナル伝達
Outline of Final Research Achievements

The expression of circadian rhythm genes, which controls the internal clock, is dysregulated in osteoarthritic cartilage. We focused on two major genes of the circadian rhythm pathway; BMAL1 and NR1D1 and showed that the expression pattern of these genes diminishes with the progression of osteoarthritis in mouse knees. Furthermore, when circadian rhythm gene expression was inhibited in cultured chondrocytes, the function of pathways that maintain homeostasis of the cell activity was altered.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症はいまだに病態が解明されておらず、予防することも根本的に治療することもできないため、疼痛を緩和するなどの対症療法しかないのが現状である。これまで関節軟骨において概日リズム遺伝子の担う役割はほとんど解明されていなかったが、本研究によりなぜ軟骨が変性し摩耗していくのかという病態の解明に一歩近づくことができた。こうした成果の蓄積により、変形性膝関節症の原因が明らかとなれば治療法の開発につながる可能性があり、さらなる研究の成果が期待される。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(2 results)

All 2017 Other

All Int'l Joint Research (1 results) Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results)

  • [Int'l Joint Research] The Scripps Research Institute(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Dysregulated circadian rhythm pathway in human osteoarthritis: NR1D1 and BMAL1 suppression alters TGF-β signaling in chondrocytes2017

    • Author(s)
      R. Akagi, Y. Akatsu, K.M. Fisch, O. Alvarez-Garcia, T. Teramura, Y. Muramatsu, M. Saito, T. Sasho, A.I. Su, M.K. Lotz
    • Journal Title

      Osteoarthritis Cartilage

      Volume: - Pages: 943-951

    • DOI

      10.1016/j.joca.2016.11.007

    • Related Report
      2017 Research-status Report 2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research

URL: 

Published: 2016-04-21   Modified: 2022-02-16  

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