Analysis of the molecular networks that regulate novel chondrogenic transcription factor, EMX2

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K09592
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokyo
• Principal Investigator: Ikeda Toshiyuki 東京大学, 医学部附属病院, 助教 (80322759)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 軟骨分化 / SOXトリオ / 選択的スプライシング / 転写因子 / サイトカイン

Outline of Final Research Achievements

Chondrogenesis by introduction of EMX2 was confirmed in several chondrogenic cell lines and human MSC by promoter-reporter assays, real-time RT PCR analyses, and ALP/alcian blue staining of cultured cells. In contrast to the SOX trio, chondrogenesis derived from EMX2 was specific to chondrogenic cells and it could not induce chondrogenesis in carcinoma cell lines. There was a short variant of EMX2 in which lacked exon 2, and this variant had weaker chondrogenic ability. RELA activated EMX2 promoter, and close relationship between EMX2 and NF-κβ signals was suggested. As chondrogenic factors that were induced by EMX2, several TNF superfamily ligands were identified.

Free Research Field

軟骨代謝学

Academic Significance and Societal Importance of the Research Achievements

軟骨分化誘導能を持つ新規転写因子EMX2を新たに同定した。EMX2はSOXトリオと異なり軟骨分化誘導能をもつ細胞種に特異的に作用し、より分化が進行した状態についての研究標的分子として有望である。またEMX2の上流・下流にNFκβシグナルが関与すること、TNFスーパーファミリーリガンドの中に軟骨分化誘導能をもつものが存在することが示唆されたことで、軟骨再生薬開発への糸口が見えてきたものと考えられる。