in vivo analysis of Mesenchymal stem cells using Runx2 conditional KO mouse

• Project/Area Number: 26460387
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pathological medical chemistry
• Research Institution: Okayama University (2016); Kanazawa University (2014-2015)
• Principal Investigator: Takarada Takeshi 岡山大学, 医歯薬学総合研究科, 准教授 (30377428)
• Co-Investigator(Renkei-kenkyūsha): Hinoi Eiichi 金沢大学, 薬学系, 准教授 (70360865)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 間葉系幹細胞 / Runx2 / 転写制御因子

Outline of Final Research Achievements

The cellular origin and essential period for Runx2 function during osteoblast differentiation in intramembranous ossification remain poorly understood. Paired related homeobox 1 (Prx1) is expressed in craniofacial mesenchyme, and Runx2 deficiency in Prx1+-derived cells (Runx2prx1－/－ mice) resulted in defective intramembranous ossification. Double-positive cells for Prx1-GFP and stem cell antigen-1 (Sca1) (Prx1+Sca1+ cells) in the calvaria expressed Runx2 at lower levels and were more homogeneous and primitive as compared with Prx1+Sca1－ cells. These findings indicate that the essential period of Runx2 function on intramembranous ossification would begin at the Prx1+Sca1+ mesenchymal stem cell stage and end at the Osx+Prx1－Sca1－ osteoblast precursor stage.

Research Products

• [Int'l Joint Research] Rush University Medical Center/University of Massachusetts(米国)
• [Int'l Joint Research] MRC/University of Edinburgh(英国)
• [Int'l Joint Research] Columbia University/The Albert Einstein College of Medicine(米国)
• [Journal Article] The transcriptional modulator interferon-related developmental regulator 1 in osteoblasts suppresses bone formation and promotes bone resorption. (2016)
  • Author(s): Takashi Iezaki, Yuki Onishi, Kakeru Ozaki, Kazuya Fukasawa, Yoshifumi Takahata, Yukari Nakamura, Koichi Fujikawa, Takeshi Takarada, Yukio Yoneda and Eiichi Hinoi
  • Journal Title: Journal of Bone and Mineral Research Volume: 31(3) Issue: 3 Pages: 573-84
  • DOI: 10.1002/jbmr.2720
  • Peer Reviewed / Open Access
• [Journal Article] Circadian Clock Regulates Bone Resorption in Mice. Circadian Clock Regulates Bone Resorption in Mice. (2016)
  • Author(s): Xu C, Ochi H, Fukuda T, Sato S, Sunamura S, Takarada T, Hinoi E, Okawa A, Takeda S.
  • Journal Title: J Bone Miner Res. Volume: - Issue: 7 Pages: 1344-1355
  • DOI: 10.1002/jbmr.2803
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] ATF3 controls proliferation of osteoclast precursor and bone remodeling. (2016)
  • Author(s): Fukasawa K, Park G, Iezaki T, Horie T, Kanayama T, Ozaki K, Onishi Y, Takahata Y, Yoneda Y, Takarada T, Kitajima S, Vacher J, Hinoi E.
  • Journal Title: Sci Rep. Volume: 6 Issue: 1 Pages: 30918-30918
  • DOI: 10.1038/srep30918
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Transcriptional Modulator Ifrd1 Regulates Osteoclast Differentiation through Enhancing the NF-κB/NFATc1 Pathway. (2016)
  • Author(s): Iezaki T, Fukasawa K, Park G, Horie T, Kanayama T, Ozaki K, Onishi Y, Takahata Y, Nakamura Y, Takarada T, Yoneda Y, Nakamura T, Vacher J, Hinoi E.
  • Journal Title: Mol Cell Biol. Volume: 36(19) Issue: 19 Pages: 2451-2463
  • DOI: 10.1128/mcb.01075-15
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Genetic analysis of Runx2 function during intramembranous ossification. (2016)
  • Author(s): Takeshi Takarada, Ryota Nakazato, Azusa Tsuchikane, Koichi Fujikawa, Takashi Iezaki, Yukio Yoneda, Eiichi Hinoi
  • Journal Title: Development Volume: 143 Pages: 211-218
  • DOI: 10.1242/dev.128793
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Upregulation of Slc38a1 gene along with promotion of neurosphere growth and subsequent neuronal specification in undifferentiated neural progenitor cells exposed to theanine. (2016)
  • Author(s): Takeshi Takarada, Masato Ogura, Noritaka Nakamichi, Takami Kakuda, Ryota Nakazato, Hiroshi Kokubo, Shinsuke Ikeno, Saki Nakamura, Takaya Kutsukake, Eiichi Hinoi and Yukio Yoneda
  • Journal Title: Neurochem Res Volume: 41 Issue: 1-2 Pages: 5-15
  • DOI: 10.1007/s11064-015-1591-4
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Potential interactions of calcium-sensitive reagents with zinc ion in different cultured cells. (2015)
  • Author(s): Koichi Fujikawa, Ryo Fukumori, Saki Nakamura, Takaya Kutsukake, Takeshi Takarada and Yukio Yoneda
  • Journal Title: PLoS ONE Volume: 10 Issue: 5 Pages: e0127421-e0127421
  • DOI: 10.1371/journal.pone.0127421
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Glucose Uptake and Runx2 Synergize to Orchestrate Osteoblast Differentiation and Bone Formation. (2015)
  • Author(s): Jianwen Wei, Junko Shimazu, Munevver P. Makinistoglu, Antonio Maurizi, Daisuke Kajimura, Haihong Zong, Takeshi Takarada, Takashi Iezaki, Jeffrey E. Pessin, Eiichi Hinoi and Gerard Karsenty
  • Journal Title: Cell Volume: 161 Issue: 7 Pages: 1576-1591
  • DOI: 10.1016/j.cell.2015.05.029
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Daily oral intake of theanine prevents the decline of 5-bromo-2'-deoxyuridine incorporation in hippocampal dentate gyrus with concomitant alleviation of behavioral abnormalities in adult mice with severe traumatic stress. (2015)
  • Author(s): Takeshi Takarada, Noritaka Nakamichi, Takami Kakuda, Ryota Nakazato, Hiroshi Kokubo, Shinsuke Ikeno, Saki Nakamura, Eiichi Hinoi and Yukio Yoneda
  • Journal Title: J Pharmacol Sci Volume: 127 Issue: 3 Pages: 292-297
  • DOI: 10.1016/j.jphs.2014.12.018
  • Peer Reviewed / Open Access
• [Journal Article] Upregulation of runt-related transcription factor-2 through CCAAT enhancer binding protein-beta signaling pathway in microglial BV-2 cells exposed to ATP. (2015)
  • Author(s): Ryota Nakazato*, Takeshi Takarada*, Shinsuke Ikeno, Saki Nakamura, Takaya Kutsukake, Eiichi Hinoi and Yukio Yoneda *Equally contributed.
  • Journal Title: J Cell Physiol. in press Volume: - Issue: 10 Pages: 2510-2521
  • DOI: 10.1002/jcp.24988
  • Peer Reviewed / Open Access
• [Journal Article] Constitutive and functional expression of runt-related transcription factor-2 by microglial cells. (2014)
  • Author(s): Ryota Nakazato, Takeshi Takarada, Takumi Watanabe, Binh Thanh Nguyen, Shinsuke Ikeno, Eiichi Hinoi, Yukio Yoneda
  • Journal Title: Neurochemistry International Volume: 74 Pages: 24-35
  • DOI: 10.1016/j.neuint.2014.04.010
  • Peer Reviewed / Open Access
• [Presentation] 創薬・再生医療を指向した幹細胞の階層法/系譜の分子理解 (2017)
  • Author(s): 宝田 剛志
  • Organizer: 第90回日本薬理学会年会
  • Place of Presentation: 長崎ブリックホール
  • Invited
• [Presentation] 組織再生を指向した間葉系幹細胞の細胞生物学的特徴づけ (2016)
  • Author(s): 宝田 剛志
  • Organizer: 組織再生セミナー（京都大学再生医科学研究所）
  • Place of Presentation: 京都大学再生医科学研究所
  • Invited
• [Presentation] 組織機能修復を指向した間葉系幹細胞の細胞生物学的特徴づけ (2016)
  • Author(s): 宝田 剛志
  • Organizer: 第153回ECM Society、第2回 Craniofacial and Stem Cell Biology Seminar
  • Place of Presentation: 岡山大学歯学部
  • Invited
• [Presentation] 遺伝子改変マウスを利用した生体内間葉系幹細胞の階層性の理解 (2016)
  • Author(s): 宝田 剛志
  • Organizer: 第72回岡山実験動物研究会例会
  • Place of Presentation: 岡山大学医学部
  • Invited
• [Presentation] 緑茶アミノ酸テアニンによる神経系前駆細胞の機能制御 (2015)
  • Author(s): 宝田 剛志
  • Organizer: 生体機能と創薬シンポジウム2015
  • Place of Presentation: 千葉
  • Year and Date: 2015-08-28
  • Invited
• [Presentation] The role of Runx2 in endochondral and intramembranous ossification during skeletogenesis. (2015)
  • Author(s): Takeshi Takarada
  • Organizer: The 3rd Seoul Symposium on Bone Health
  • Place of Presentation: Seoul (Korea)
  • Year and Date: 2015-05-28
  • Int'l Joint Research / Invited
• [Presentation] 神経細胞毒性におけるグルタミントランスポーターSlc38a1の役割 (2015)
  • Author(s): 宝田 剛志、中里 亮太、中村 早希、藤川 晃一、高 巳奇、檜井 栄一、米田 幸雄
  • Organizer: 第88回日本薬理学会年会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-03-18 – 2015-03-20
• [Presentation] 脳梗塞後神経細胞障害におけるグルタミントランスポーターSlc38a1の役割 (2014)
  • Author(s): 宝田 剛志、中里 亮太、中村 早希、藤川 晃一、高 巳奇、檜井 栄一、米田 幸雄
  • Organizer: 第126回日本薬理学会近畿部会
  • Place of Presentation: 和歌山
  • Year and Date: 2014-10-24
• [Presentation] 骨関節組織におけるアミノ酸シグナルの役割 (2014)
  • Author(s): 宝田 剛志
  • Organizer: 福島県立医科大学研究連携セミナー2014
  • Place of Presentation: 福島
  • Year and Date: 2014-07-04
  • Invited
• [Presentation] Skeletal phenotypes of Runx2 conditional knockout mice. (2014)
  • Author(s): Takeshi Takarada, Ryota Nakazato, Azusa Tsuchikane, Eiichi Hinoi, Yukio Yoneda
  • Organizer: The 12th Annual Meeting of the International Society for Stem Cell Reserch (ISSCR)
  • Place of Presentation: Vancouver, Canada
  • Year and Date: 2014-06-18 – 2014-06-21
• [Remarks] 骨が作られる仕組みを解明！
  • URL: http://www.kanazawa-u.ac.jp/wp-content/uploads/2015/12/151215.pdf