Establishment of a novel screening system to isolate PTH-like osteogenic small compounds

• Project/Area Number: 24659824
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• 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(Kenkyū-buntansha): HATA Kenji 大阪大学, 大学院歯学研究科, 准教授 (80444496)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: PTH / 骨形成 / スクリーニング / 骨芽細胞

Research Abstract

Parathyroid hormone (PTH) has been shown to be a effective therapeutic agents for bone diseases such as osteoporosis. However, PTH has two major problems; high cost and limitation of term due to its possible side effect. Thus, we have attempted to contribute to development of screening systems that can allow us to explore the small compounds to mimic osteogenic action of PTH. We found that an osteoblastic cell line, SaOS2, is useful and suitable for the screening system. We also attempted to identify the target genes of PTH. Our data suggest that Wnt5a would be a target gene of PTH during bone formation. Our study suggest that a screening system in which we can determine the Wnt5a gene promoter activity would be helpful for developing the therapeutic bone forming small compounds.

Research Products

• [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 Pages: 1-12
• [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] 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] Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes (2013)
  • Author(s): Hisada K, Hata K, Ichida F, Matsubara T, Orimo H, Nakano T, Yatani H, Nishimura R*, Yoneda T
  • Journal Title: J Bone Miner Metab Volume: 31 Issue: 1 Pages: 53-63
  • DOI: 10.1007/s00774-012-0385-x
  • NAID: 10031168837
  • Peer Reviewed
• [Journal Article] 骨代謝調節機構におけるシグナル伝達と転写制御の役割 (2013)
  • Author(s): 西村理行
  • Journal Title: 大阪大学歯学雑誌 Volume: 58 Pages: 1-1
• [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
• [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] Retinoic acid regulates commitment of undifferentiated mesenchymal stem cells into osteoblasts and adipocytes. (2013)
  • Author(s): Hisada K, Hata K, Ichida F, Matsubara T, Orimo H, Nakano T, Yatani H, Nishimura R, Yoneda T
  • Journal Title: J Bone Miner Metab Volume: 31 Pages: 53-63
  • NAID: 10031168837
  • Peer Reviewed
• [Journal Article] Regulation of endochondral ossification by transcription factors (2012)
  • Author(s): Nishimura R, Hata K, Ono K, Amano K, Takigawa Y, Wakabayashi M, Takashima R, Yoneda T
  • Journal Title: Frontiers in Biosci-Landmark Volume: 17 Pages: 2657-2666
• [Journal Article] Regulation of endochondral ossification by transcription factors (2012)
  • Author(s): Nishimura R, Hata K, Ono K, Takashima R, Yoshida M, Yoneda T
  • Journal Title: J Oral Biosciences Volume: 54 Pages: 180-183
• [Presentation] Forkhead protein FoxC1 regulates chondrogenic genes expression bymodulating Ihh/Gli2 signaling (2013)
  • Author(s): Yoshida M, Hata K, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: The American Society for Bone and Mineral Research 35th Annual Meeting
  • Place of Presentation: Baltimore Maryland, USA
  • Year and Date: 2013-10-04
• [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シンポジウム
  • Place of Presentation: 岡山コンベンションセンター
  • Year and Date: 2013-09-22
• [Presentation] Regulation of Endochondral Ossification by Transcription Factor (2013)
  • Author(s): Nishimura R
  • Organizer: 10th Bone Biology Forum
  • Place of Presentation: Fuji Institute of Education and Training
  • Year and Date: 2013-08-23
• [Presentation] The transcription factor FoxC1 up-regulates PTHrP expression together with Gli2 in chondrocytes (2013)
  • Author(s): Yoshida M, Hata K, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: 2^<nd> Joint Meeting of the International Bone and Mineral Society and The Japanese Society for Bone and Mineral Research
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2013-05-29
• [Presentation] 転写因子Arid5bはSox9標的遺伝子プロモーター領域のヒストン脱メチル化を介して軟骨細胞分化を促進する (2013)
  • Author(s): 波多賢二、高島利加子、Whitson RH、西村理行、米田俊之
  • Organizer: 軟骨代謝学会シンポジウム第26回日本軟骨代謝学会
  • Place of Presentation: 千里ライフサイエンスセンター
  • Year and Date: 2013-03-01
• [Presentation] Regulation of Endochondral Ossification by Transcription Factor (2013)
  • Author(s): Riko Nishimura
  • Organizer: 10th Bone Biology Forum
  • Place of Presentation: 富士研修所（裾野市、静岡県）
  • 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（岡山市）
  • Invited
• [Presentation] Arid5a is an IL-6 mRNA stability protein. Chlorpromazine mediates its inhibitory effect on IL-6 production in macrophages through inhibition of Arid5a expression (2012)
  • Author(s): Masuda K, Barry R, Nishimura R, Takeuchi O, Takashi M, Daron S, Kishimoto T
  • Organizer: 第41回免疫学会学術集会シンポジウム
  • Place of Presentation: 神戸国際会議場
  • Year and Date: 2012-12-07
• [Presentation] The Transcription Factor FoxC1 Regulates Chondrogenesis Together with Gli2 through Induction of PTHrP (2012)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: American Society for Bone and Mineral Research Annual Meeting
  • Place of Presentation: Minneapolis, USA
  • Year and Date: 2012-10-12
• [Presentation] The transcription factor FoxC1 regulates chondrogenesis together with Gli2 through induction of PTHrP (2012)
  • Author(s): Yoshida M, Hata K, Takashima R, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: Australian & New Zealand Bone & Mineral Society 22nd Annual Scientific Meeting in conjunction with 1^<st> Asia-Pacific Bone and Mineral Research Meeting
  • Place of Presentation: Pan Pacific Hotel, Perth, Western Australia
  • Year and Date: 2012-09-04
• [Presentation] 軟骨細胞分化のエピゲノム (2012)
  • Author(s): 波多賢二、高島利加子、西村理行、米田俊之
  • Organizer: 日本骨代謝学会学術集会
  • Place of Presentation: 京王プラザホテル
  • Year and Date: 2012-07-19
• [Presentation] 骨格形成過程における転写因子ネットワークの制御機構 (2012)
  • Author(s): 西村理行
  • Organizer: 第66回口腔科学会教育研修会
  • Place of Presentation: リーガロイヤルホテル広島
  • Year and Date: 2012-05-16
• [Presentation] 軟骨細胞分化のエピゲノム (2012)
  • Author(s): 波多 賢二、高島 利加子、西村 理行、米田 俊之．
  • Organizer: 日本骨代謝学会
  • Place of Presentation: 京王プラザホテル
  • Invited