Functional role and regulatory mechanism of transcription factor Osterix in skeletal development

• Project/Area Number: 25293378
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Functional basic dentistry
• Research Institution: Osaka University
• Principal Investigator: Nishimura Riko 大阪大学, 歯学研究科(研究院), 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2015: ¥6,760,000 (Direct Cost: ¥5,200,000、Indirect Cost: ¥1,560,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2013: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
• Keywords: 骨 / 軟骨 / 転写因子 / Osterix / エピゲノム

Outline of Final Research Achievements

Although Osterix is an essential transcription factor for membranous and endochondral ossification, Osterix knockout mice show both membranous and endochondral ossification at E18.5 days. We attempted to identify transcription factor that compensate osteogenic action of Osterix, and isolated a Sp1 family member transcription factor as a candidate. This Sp1 family member transcription factor was induced by BMP2 treatment. In addition, the Sp1 family member transcription factor showed similar function to Osterix in vitro. To understand the role of the Sp1 family member transcription factor in bone formation, we generated double knockout mice of Osterix and the Sp1 family member transcription factor, and examined the mice. The double knockout mice showed both membranous and endochondral ossification at E18.5 days. The data suggest that other molecule is involved in membranous and endochondral ossification.

Research Products

• [Journal Article] The transcription factor Foxc1 is necessary for Ihh-Gli2-regulated endochondral ossification (2015)
  • Author(s): Yoshida M, Hata K, Takashima R, Ono K, Nakamura E, Takahata Y, Murakami T, Iseki S, Takano-Yamamoto T, Nishmura R, Yoneda T
  • Journal Title: NATURE COMMUNICATIONS Volume: 6:6653 Issue: 1 Pages: 1-15
  • DOI: 10.1038/ncomms7653
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Regulation of transcriptional network system during bone and cartilage development. (2015)
  • Author(s): Nishimura R, Hata K, Ikeda F, Matsubara T, Amano K, Ono K, Takigawa Y, Takashima R, Yoshida M, Nakamura E, Yoneda T.
  • Journal Title: J Oral Bioscience Volume: 57 Pages: 165-170
  • Peer Reviewed
• [Journal Article] Dlx5 and Mef2 Regulate a Novel Runx2 Enhancer for Osteoblast-Specific Expression. (2014)
  • Author(s): Kawane T, Komori H, Liu W, Moriishi T, Miyazaki T, Mori M, Matsuo Y, Takada Y, Izumi S, Jiang Q, Nishimura R, Kawai Y, Komori T.
  • Journal Title: Journal of bone and mineral research Volume: - Issue: 9 Pages: 1960-1969
  • DOI: 10.1002/jbmr.2240
  • Peer Reviewed
• [Journal Article] Indian Hedgehog Signaling Regulates Transcription and Expression of Collagen Type X via Runx2/Smads Interactions. (2014)
  • Author(s): Amano K, Densmore M, Nishimura R, Lanske B.
  • Journal Title: J Biol Chem Volume: 289 Issue: 36 Pages: 24898-24910
  • DOI: 10.1074/jbc.m114.570507
  • Peer Reviewed
• [Journal Article] Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo. (2013)
  • Author(s): Kazuya Masuda, Barry Ripley, Riko Nishimura, Takashi Mino, Osamu Takeuchi, Go Shioi, Hiroshi Kiyonari, and Tadamitsu Kishimoto
  • Journal Title: Proceeding of the National Academy of Sciences of the United States of America Volume: 110 Issue: 23 Pages: 9409-9414
  • DOI: 10.1073/pnas.1307419110
  • Peer Reviewed
• [Journal Article] Arid5b facilitates chondrogenesis by recruiting the histone demethylase Phf2 to Sox9-regulated genes (2013)
  • Author(s): Hata K, Takashima R, Amano K, Ono K, Nakanishi M, Yoshida M, Wakabayashi M, Matsuda A, Maeda Y, Suzuki Y, Sugano S, Whitson RH, Nishimura R and Yoneda T
  • Journal Title: Nature communications Volume: 4 Issue: 1 Pages: 2850-2860
  • DOI: 10.1038/ncomms3850
  • Peer Reviewed
• [Journal Article] ZFHX4 interacts with the NuRD core member CHD4 and regulates the glioblastoma tumor initiating cell state. (2013)
  • Author(s): Chudnovsky Y, Kim D, Zheng S, Whyte WA, Bansal M, Bray M, Gopal S, Theisen MA, Bilodeau S, Thiru P, Muffat J, Yilmaz OH, Mitalipova M, Woolard K, Lee J, Nishimura R, Sakata N, Fine HA, Carpenter AE, Silver SJ, Verhaak RGW, Califano A, Young RA, Ligon KL, Mellinghoff IK, Root DE, Sabatini DM, Hahn WC, Chheda MG
  • Journal Title: Cell Reports Volume: 6 Issue: 2 Pages: 1-12
  • DOI: 10.1016/j.celrep.2013.12.032
  • Peer Reviewed
• [Journal Article] 骨および軟骨の発生ならびに疾患における転写制御機構の変動． (2013)
  • Author(s): 西村 理行、波多 賢二、高島 利加子、吉田 倫子、中村 恵理子、木田 淳平、八木 寛子
  • Journal Title: Clinical Calcium Volume: 23 Pages: 1585-1593
• [Presentation] Regulation of endochondral ossification by transcription factors (2015)
  • Author(s): Nishimura R
  • Organizer: International Symposium 2015 Oral and Craniofacial Development and Diseases
  • Place of Presentation: 大阪大学（大阪府吹田市）
  • Year and Date: 2015-12-10
  • Int'l Joint Research / Invited
• [Presentation] 転写因子Foxc1はIhh-Gli2シグナルを促進し内軟骨性骨形成を制御する (2015)
  • Author(s): 波多 賢二、吉田 倫子、中村 恵理子、高畑 佳史、村上 智彦、井関 祥子、山本 照子、西村 理行
  • Organizer: 第57回歯科基礎医学会学術大会
  • Place of Presentation: 朱鷺メッセ（新潟県新潟市）
  • Year and Date: 2015-09-11
• [Presentation] 転写因子Zfhx4はOsterixと結合して内軟骨性骨形成の後期過程を制御する (2015)
  • Author(s): 中村 恵理子、波多 賢二、吉田 倫子、村上 智彦、高畑 佳史、阿部 真土、米田 俊之、西村 理行
  • Organizer: 第33回日本骨代謝学会
  • Place of Presentation: 京王プラザホテル東京（東京都新宿区）
  • Year and Date: 2015-07-23
• [Presentation] 骨形成過程における転写制御プログラムの統合的理解の解明 (2014)
  • Author(s): 西村 理行
  • Organizer: 歯科基礎医学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-09-26
  • Invited
• [Presentation] Regulation of Endochondral Ossification by Transcription Factor (2013)
  • Author(s): Riko Nishimura
  • Organizer: 10th Bone Biology Forum
  • Place of Presentation: 富士教育研修所
  • Invited
• [Presentation] 転写ネットワークによる内軟骨性骨形成の制御機構 (2013)
  • Author(s): 西村 理行
  • Organizer: 第55回歯科基礎医学会学術大会
  • Place of Presentation: 岡山コンベンションセンター
  • Invited