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2021 Fiscal Year Annual Research Report

The study of a novel Runx2 target, Tem8, in skeletal development and chondrocyte apoptosis

Research Project

Project/Area Number 20K18460
Research InstitutionNagasaki University

Principal Investigator

姜 晴  長崎大学, 医歯薬学総合研究科(歯学系), 助教 (00790007)

Project Period (FY) 2020-04-01 – 2022-03-31
KeywordsTem8 / Runx2 / chondrocyte / proliferation / apoptosis
Outline of Annual Research Achievements

We published one paper:
Antxr1, Which Is a Target of Runx2, Regulates Chondrocyte Proliferation and Apoptosis.
To identify Runx2 target genes in chondrocytes, we introduced Runx2-expressing adenovirus or green fluorescent protein (GFP)-expressing adenovirus into Runx2 knockout primary chondrocytes and examined the differentially expressed genes by microarray. We found that Antxr1(Tem8)was directly regulated by Runx2.
To investigate whether Tem8 expression is directly regulated by Runx2, we examined Runx2-binding regulatory regions in the Tem8 region by reanalyzing our previously published chromatin immunoprecipitation (ChIP)-seq data. In a reporter assay, Runx2 enhanced the reporter activity of 1.0-kb promoter-luciferase-0.85-kb enhancer construct. In addition, ChIP analysis using Runx2 antibody demonstrated that Runx2 binds to both Runx2-binding motifs in the 0.85-kb region. This suggested that Runx2 regulates Tem8 expression mainly through the 0.85-kb enhancer.
Further, we generated Tem8 knockout mice and chondrocyte-specific Tem8 transgenic mice. In skeletal development, the limbs of Tem8 knockout mice were shorter than wild-type mice. Tem8 transgenic mice exhibited shortened limbs. BrdU-uptake and apoptosis were both increased in chondrocytes, and the apoptosis-high regions were mineralized. These findings indicated that Tem8, of which the expression is regulated by Runx2, plays an important role in chondrocyte proliferation and that overexpression of Tem8 causes chondrocyte apoptosis accompanied by matrix mineralization.

  • Research Products

    (2 results)

All 2021

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

  • [Journal Article] Runt‐related transcription factor‐2 (Runx2) is required for bone matrix protein gene expression in committed osteoblasts in mice2021

    • Author(s)
      Qin Xin、Jiang Qing、Komori Hisato、Sakane Chiharu、Fukuyama Ryo、Matsuo Yuki、Ito Kosei、Miyazaki Toshihiro、Komori Toshihisa
    • Journal Title

      Journal of Bone and Mineral Research

      Volume: 36 Pages: 2081~2095

    • DOI

      10.1002/jbmr.4386

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Runx2はマウスの骨芽細胞分化後の骨基質蛋白質遺伝子発現に必要である2021

    • Author(s)
      Qing Jiang
    • Organizer
      第39回日本骨代謝学会学術集会

URL: 

Published: 2022-12-28  

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