The mechanism of transcriptional factor Runx1 in chondrogenic differentiation

2013 Fiscal Year Final Research Report

• Project/Area Number: 22689052
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Surgical dentistry
• Research Institution: The University of Tokyo
• Principal Investigator: YANO Fumiko 東京大学, 医学(系)研究科(研究院), 助教 (80529040)
• Project Period (FY): 2010-04-01 – 2013-03-31
• Keywords: Runx1 / 変形性膝関節症 / 軟骨分化

Research Abstract

To investigate the role of transcriptional factor Runx1 in chondrogenic differentiation, we analyzed the function of Runx1 from early differentiation to hypetrophy in chondrocytes in vitro and in vivo. Runx1 directly binds to COL2A1 promoter and enhances Col2a1 expression but inhibits Col10a1 expression. Runx1 is an inducer of chondrogenic differentiation and a suppressor of the subsequent hypertrophy. Runx1 is expressed in articular cartilage surface of normal tissues, but not in degradated cartilage.

Research Products

• [Journal Article] Generation of Col2a1-EGFP iPS cells for monitoring chondrogenic differentiation (2013)
  • Author(s): Saito T, Yano F, Mori D, Ohba S, Hojo H, Otsu M, Eto K, Nakauchi H, Tanaka S, Chung UI, Kawaguchi H
  • Journal Title: PLoS One Volume: 16;8(9) Pages: e74137
  • DOI: 10.1371/journal.pone.0074137
  • Peer Reviewed
• [Journal Article] Cell-sheet technology combined with a thienoindazole derivative small compound TD-198946 for cartilage regeneration (2013)
  • Author(s): Yano F, Hojo H, Ohba S, Saito T, Honnami M, Mochizuki M, Takato T, Kawaguchi H, Chung UI
  • Journal Title: Biomaterials Volume: 34(22) Pages: 5581-5587
  • DOI: 10.1016/j.biomaterials.2013.04.008
  • Peer Reviewed
• [Journal Article] Tenomodulin expression in the periodontal ligament enhances cellular adhesion (2013)
  • Author(s): Komiyama Y, Ohba S, Shimohata N, Nakajima K, Hojo H, Yano F, Takato T, Docheva D, Shukunami C, Hiraki Y, Chung UI
  • Journal Title: PLoS One Volume: 8(4) Pages: e60203
  • DOI: 10.1371/journal.pone.0060203
  • Peer Reviewed
• [Journal Article] Hedgehog-Gli activators direct osteo-chondrogenic function of bone morphogenetic protein toward osteogenesis in the perichondrium (2013)
  • Author(s): Hojo H, Ohba S, Taniguchi K, Shirai M, Yano F, Saito T, Ikeda T, Nakajima K, Komiyama Y, Nakagata N, Suzuki K, Mishina Y, Yamada M, Konno T, Takato T, Kawaguchi H, Kambara H, Chung UI
  • Journal Title: J Biol Chem. Volume: 288(14) Pages: 9924-9932
  • DOI: 10.1074/jbc.M112.409342
  • Peer Reviewed
• [Journal Article] β -Catenin regulates PTH/PTHrP receptor signals and chondrocyte hypertrophy through binding to its intracellular C-terminal region (2013)
  • Author(s): Yano F, Saito T, Ogata N, Yamazawa T, Iino M, Chung UI, Kawaguchi H
  • Journal Title: Arthritis Rheum Volume: 65(2) Pages: 429-435
  • DOI: 10.1136/annrheumdis-2012-201745
  • Peer Reviewed
• [Journal Article] A novel disease-modifying osteoarthritis drug candidate targeting Runx1 (2013)
  • Author(s): Yano F, Hojo H, Ohba S, Fukai A, Hosaka Y, Ikeda T, Saito T, Hirata M, Chikuda H, Takato T, Kawaguchi H, Chung UI
  • Journal Title: Ann Rheum Dis. Volume: 72(5) Pages: 748-753
  • DOI: 10.1136/annrheumdis-2012-201745
  • Peer Reviewed
• [Journal Article] Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein (BMP) signaling. Nanog promotes osteogenic differentiation of the mouse mesenchymal cell line C3H10T1/2 by modulating bone morphogenetic protein (BMP) signaling (2013)
  • Author(s): Ogasawara T, Ohba S, Yano F, Kawaguchi H, Chung UI, Saito T, Yonehara Y, Nakatsuka T, Mori Y, Takato T, Hoshi K
  • Journal Title: J Cell Physiol Volume: 228(1) Pages: 163-171
  • DOI: 10.1002/jcp.24116
  • Peer Reviewed
• [Journal Article] Trehalose treatment suppresses inflammation, oxidative stress, and vasospasm induced by experimental subarachnoid hemorrhage (2012)
  • Author(s): Echigo R, Shimohata N, Karatsu K, Yano F, Kayasuga-Kariya Y, Fujisawa A, Ohto T, Kita Y, Nakamura M, Suzuki S, Mochizuki M, Shimizu T, Chung UI, Sasaki N
  • Volume: 10
  • Pages: 80
  • DOI: 10.1186/1479-5876-10-80
  • Peer Reviewed
• [Journal Article] Gli1 protein participates in Hedgehog-mediated specification of osteoblast lineage during endochondral ossification (2012)
  • Author(s): Hojo H, Ohba S, Yano F, Saito T, Ikeda T, Nakajima K, Komiyama Y, Nakagata N, Suzuki K, Takato T, Kawaguchi H, Chung U
  • Journal Title: J Biol Chem. Volume: 287(21) Pages: 17860-17869
  • DOI: 10.1074/jbc.M112.347716
  • Peer Reviewed
• [Journal Article] C/EBPβ and RUNX2 cooperate to degrade cartilage with MMP-13 as the target and HIF-2α as the inducer in chondrocytes (2012)
  • Author(s): Hirata M, Kugimiya F, Fukai A, Saito T, Yano F, Ikeda T, Mabuchi A, Sapkota BR, Akune T, Nishida N, Yoshimura N, Nakagawa T, Tokunaga K, Nakamura K, Chung UI, Kawaguchi H
  • Journal Title: Hum Mol Genet. Volume: 21(5) Pages: 1111-1123
  • DOI: 10.1093/hmg/ddr540
  • Peer Reviewed
• [Journal Article] Coordination of chondrogenesis and osteogenesis by hypertrophic chondrocytes in endochondral bone development (2010)
  • Author(s): Hojo H, Ohba S, Yano F, Chung UI
  • Journal Title: J Bone Miner Metab. Volume: 28(5) Pages: 489-502
  • DOI: 10.1007/s00774-010-0199-7
  • Peer Reviewed
• [Journal Article] Trehalose inhibits oral dryness by protecting the cell membrane (2010)
  • Author(s): Mori Y, Yano F, Shimohata N, Suzuki S, Chung UI, Takato T
  • Journal Title: Int J Oral Maxillofac Surg Volume: 39(9) Pages: 916-921
  • DOI: 10.1016/j.ijom.2010.04.047
  • Peer Reviewed
• [Journal Article] Transcriptional regulation of endochondral ossification by HIF-2alpha during skeletal growth and osteoarthritis development (2010)
  • Author(s): Saito T, Fukai A, Mabuchi A, Ikeda T, Yano F, Ohba S, Nishida N, Akune T, Yoshimura N, Nakagawa T, Nakamura K, Tokunaga K, Chung UI, Kawaguchi H
  • Journal Title: Nat Med. Volume: 16(6) Pages: 678-686
  • DOI: 10.1038/nm.2146
  • Peer Reviewed
• [Journal Article] Enhancement of bone formation ex vivo and in vivo by a helioxanthin-derivative (2010)
  • Author(s): Nakajima K, Komiyama Y, Hojo H, Ohba S, Yano F, Nishikawa N, Aburatani H, Takato T, Chung UI
  • Journal Title: Biochem Biophys Res Commun. Volume: 397(3) Pages: 631
  • DOI: 10.1016/j.bbrc.2010.04.041
  • Peer Reviewed
• [Journal Article] Identification of oxytetracycline as a chondrogenic compound using a cell-based screening system (2010)
  • Author(s): Hojo H, Yano F, Ohba S, Igawa K, Nakajima K, Komiyama Y, Kan A, Ikeda T, Yonezawa T, Woo JT, Takato T, Nakamura K, Kawaguchi H, Chung UI
  • Journal Title: J Bone Miner Metab. Volume: 28(6) Pages: 627-633
  • DOI: 10.1007/s00774-010-0179-y
  • Peer Reviewed
• [Journal Article] Akt1 in chondrocytes controls cartilage calcification during endochondral ossification under physiological and pathological conditions (2010)
  • Author(s): Fukai A, Kawamura N, Saito T, Oshima Y, Ikeda T, Kugimiya F, Higashikawa H, Yano F, Ogata N, Nakamura K, Chung UI, and Kawaguchi H
  • Journal Title: Arthritis Rheum Volume: 62(3) Pages: 826-836
  • DOI: 10.1002/art.27296
  • Peer Reviewed
• [Journal Article] Runx1 and Runx2 cooperate during sternal morphogenesis (2010)
  • Author(s): Kimura A, Inose H, Yano F, Fujita K, Ikeda T, Sato S, Iwasaki M, Jinno T, Ae K, Fukumoto S, Takeuchi Y, Itoh H, Imamura T, Kawaguchi H, Chung UI, Martin JF, Iseki S, Shinomiya K, Takeda S
  • Journal Title: Development Volume: 137(7) Pages: 1159-1167
  • DOI: 10.1242/dev.045005
  • Peer Reviewed
• [Presentation] 新規OA治療候補化合物はRunx1 をターゲットとしている (2014)
  • Author(s): 矢野文子, 北條宏徳, 大庭伸介, 深井厚,保坂陽子,池田敏之, 斎藤琢, 平田真, 筑田博隆,高戸毅, 川口浩, 鄭雄一
  • Organizer: 第27回日本軟骨代謝学会
  • Place of Presentation: 京都府医師会館、京都(第19回日本軟骨代謝学会賞受賞口演)
  • Year and Date: 20140228-0301
• [Presentation] 新規OA治療候補化合物はRunx1 をターゲットとしている (2014)
  • Author(s): 矢野文子, 保坂陽子,斎藤琢, 北條宏徳,大庭伸介, 高戸毅, 鄭雄一
  • Organizer: FIRST 合同国際シンポジウム
  • Place of Presentation: 東京大学 伊藤国際学術研究センター 伊藤謝恩ホール、東京(査読なし、口頭・ポスター発表)
  • Year and Date: 2014-02-21
• [Presentation] 変形性関節症の新規治療候補薬の発見 (2014)
  • Author(s): 矢野文子, 大庭伸介, 鄭雄一
  • Organizer: 東大病院先端医療開発フォーラム
  • Place of Presentation: 東京大学 伊藤国際学術研究センター伊藤謝恩ホール、東京(査読なし、口頭・ポスター発表)
  • Year and Date: 2014-01-24
• [Presentation] A novel disease-modifying osteoarthritis drug candidate targeting Runx1 (2013)
  • Author(s): Fumiko Yano, Yoko Hosaka, Atsushi Fukai, Taku Saito, Hironori Hojo, Shinsuke Ohba, Hiroshi Kawaguchi, Tsuyoshi Takato, Ung-il Chung
  • Organizer: Frontiers 2013 EPFL Symposium
  • Place of Presentation: Swiss Federal Institute of Technology in Lausanne, Lausanne, Switzerland (査読なし、ポスター発表)
  • Year and Date: 20130621-22
• [Presentation] novel disease-modifying osteoarthritis drug candidate targeting Runx1 (2013)
  • Author(s): Fumiko Yano, Yoko Hosaka, Atsushi Fukai, Taku Saito, Hironori Hojo, Shinsuke Ohba, Hiroshi Kawaguchi, Tsuyoshi Takato, Ung-il Chung
  • Organizer: 第13回東京大学生命科学シンポジウム
  • Place of Presentation: 東京大学 伊藤国際学術研究センター 伊藤謝恩ホール、東京(査読なし、口頭・ポスター発表)
  • Year and Date: 2013-06-08
• [Presentation] Prevention and Repair of Cartilage Degeneration by A Novel Small Thienoindazole-Derivative Compound (2012)
  • Author(s): Fumiko Yano, Hironori Hojo, Shinsuke Ohba, Yoko Hosaka, Atsushi Fukai, Taku Saito, Hiroshi Kawaguchi, Ung-il Chung
  • Organizer: 1^<st> Joint Symposium 2012 Bridging Cancer Nanotechnology
  • Place of Presentation: The University of Texas MD Anderson Cancer Center, Houston, Texas (査読なし、ポスター発表)
  • Year and Date: 20120813-14
• [Presentation] 細胞シート工学を用いた新規軟骨再生誘導剤による膝関節軟骨再生法の開発 (2012)
  • Author(s): 矢野文子, 北條宏徳, 大庭伸介, 池田敏之, 斎藤琢, 本阿彌宗紀、平田真、筑田博隆、望月学、佐々木伸雄、高戸毅, 川口浩, 鄭雄一
  • Organizer: 第11回日本再生医療学会総会
  • Place of Presentation: パシフィコ横浜、神奈川 (若手研究奨励賞受賞者講演)
  • Year and Date: 20120612-14
• [Presentation] Prevention and repair of cartilage degeneration by a novel thienoindazole-derivative compound (2012)
  • Author(s): Fumiko Yano, Yoko Hosaka, Atsushi Fukai, Taku Saito, Hironori Hojo, Shinsuke Ohba, Hiroshi Kawaguchi, Ung-il Chung
  • Organizer: 2012 World Congress on Osteoarthritis (OARSI)
  • Place of Presentation: Barcelona, Spain (査読有・ポスター発表)
  • Year and Date: 20120400
• [Presentation] 新規低分子化合物チエノインダゾール誘導体はRunx1 とSox trio を介して関節軟骨再生を誘導する (2011)
  • Author(s): 矢野文子, 北條宏徳, 大庭伸介, 池田敏之, 斎藤琢, 高戸毅, 川口浩, 鄭雄一
  • Organizer: 第24回日本動物細胞工学会
  • Place of Presentation: 東京大学本郷キャンパス 山上会館、東京(査読有・ポスター発表)
  • Year and Date: 20110722-23
• [Presentation] A Novel Thienoindazole-Derivative Small Compound Induces Chondrogenic Differentiation without Promoting Hypertrophy through Runx1 (2010)
  • Author(s): Fumiko Yano
  • Organizer: 7th Meeting of Bone Biology Forum 2010
  • Place of Presentation: Fuji Institute of Education and Training, Shizuoka
  • Year and Date: 20100800
  • Invited
• [Book] 細胞シート工学を用いた新規軟骨再生誘導剤による関節軟骨再生法の開発 (Clinical Calcium vol21. No.6) (2011)
  • Author(s): 矢野文子, 北條宏徳, 鄭雄一
  • Total Pages: 75-82
• [Remarks] 鄭雄一研究室 大庭・矢野・鄭グループ
  • URL: http://www.tetrapod.t.u-tokyo.ac.jp/med/