Investigation of transcriptional network system of chondrocytes by novel gene-editing cloning technique

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K15779
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: Nishimura Riko 大阪大学, 歯学研究科, 教授 (60294112)
• Co-Investigator(Renkei-kenkyūsha): HATA KENJI 大阪大学, 大学院歯学研究科, 准教授 (80444496) ; MURAKAMI TOMOHIKO 大阪大学, 大学院歯学研究科, 講師 (50510723)
• Research Collaborator: TAKAHATA YOSHIFUMI 大阪大学, 大学院歯学研究科, 助教 (60635845)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 軟骨細胞 / 転写因子 / ゲノム編集

Outline of Final Research Achievements

Transcription factors, Sox9, Runx2 and Osterix play critical and central roles in chondrocyte differentiation. It is also getting clearer how these transcription factors regulate chondrocytes differentiation through complex formation with several transcriptional regulators. In contrast, molecular mechanisms that controls expression of Sox9 and Runx2 have been still known. We found that bone morphogenetic protein 2 (BMP2) induced several early-responsive genes expression along with chondrocyte differentiation. To address the mechanisms, we attempted to establish a gene cloning approach based on Cas9 genome editing system. Using the established gene cloning system, we successfully isolated the transcription factor that directly interacts with the BMP2-responseive gene promoter region. Interestingly, we found that the expression of the transcription factor is regulated by ubiquitin-proteasome system. Moreover, we observed that the knockout mice of the transcription factor showed dwarf.

Free Research Field

分子生物学