• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Mechanism of chondorogenic differentiation from aged mesencymal stem cells by overexpression of delta133p53

Research Project

Project/Area Number 18H02925
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 56020:Orthopedics-related
Research InstitutionAkita University (2020-2021)
Kyoto University (2018-2019)

Principal Investigator

Fujita Kaori  秋田大学, 理工学研究科, 講師 (10633092)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2021: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2020: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
KeywordsΔ133p53 / p53 isoform / aging / mesencymal stem cells / differentiation / chondrocytes / delta133p53 / 間葉系幹細胞老化 / 軟骨細胞分化 / 細胞老化 / p53 / p53 isoforms / 間葉系幹細胞 / 軟骨細胞 / 老化 / シグナル伝達 / 分化誘導 / 増殖 / 抗老化 / 軟骨細胞への分化誘導 / 軟骨細胞増殖
Outline of Final Research Achievements

For therapeutic applications against defects of adult articular cartilage increase with aging, development of regenerative medicine and cartilage tissue engineering are important. However, autologous bone marrow mesenchymal stromal cell (MSC) implantation for elderly individuals is more difficult than young individuals, because capability of cell proliferation and differentiation of the cells decreases in elderly individuals. Cellular senescence contributes to organismal aging and age-related diseases. The p53 signaling network plays a critical role in the induction of cellular senescence. The human TP53 gene encodes twelve natural isoforms. Overexpressing Δ133p53, an anti-senescence p53 isoform, in near-senescent hMSCs and their differentiated chondrocytes showed characteristic differential expression genes in RNA-sequencing. We also obtained many Δ133p53-transcriptional target genes during the chondrogenic differentiation from Δ133p53-overexpressing hMSCs, by Cut & Run-sequencing.

Academic Significance and Societal Importance of the Research Achievements

変形性関節症をはじめとする軟骨の加齢性疾患に対する根本的な治療は現在はない。軟骨には血管も神経も通っておらず、自然治癒も期待できない。変形性関節症の罹患率の高い高齢患者からの間葉系幹細胞を用いた再生医療を考える場合、高齢患者の細胞は老化しており、軟骨細胞に分化誘導させることは若年の患者の細胞に比べて非常に困難である。一方、自分の細胞を用いるという点では、拒絶反応の問題がクリアできる。以上より、既に見出した抗老化作用を持つΔ133p53を用いて老化間葉系幹細胞を若返らせ、軟骨細胞に分化誘導する詳細な分子機序を解明するために上記研究を行った。さらに詳細な解析により、誘導法の確立を目指す。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (2 results)

All 2019

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

  • [Journal Article] p53 Isoforms in Cellular Senescence- and Ageing-Associated Biological and Physiological Functions.2019

    • Author(s)
      Kaori Fujita
    • Journal Title

      Int J Mol Sci.

      Volume: 20 Issue: 23 Pages: 6023-6023

    • DOI

      10.3390/ijms20236023

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] p53 isoforms in cellular senescence, aging, cancer, and reprogramming2019

    • Author(s)
      Kaori Fujita
    • Organizer
      第42回日本分子生物学会年会ワークショップ
    • Related Report
      2019 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2023-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi