Moleculr mechanism of CTGF and Odz3 in biological response of sutures to tensile force

• Project/Area Number: 26463084
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Tohoku University
• Principal Investigator: Takeshita Nobuo 東北大学, 歯学研究科, 助教 (50431515)
• Co-Investigator(Kenkyū-buntansha): 千田 透子 東北大学, 歯学研究科, 大学院非常勤講師 (40647947)
• Co-Investigator(Renkei-kenkyūsha): RYUSHI KATO 東北大学, 大学院歯学研究科, 大学院非常勤講師 (90706699)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 縫合 / CTGF / 牽引力 / メカニカルストレス / 血管形成 / 骨形成

Outline of Final Research Achievements

We have analyzed the function of CTGF during biological response of cranial sutures to tensile force. Tensile force induced the expression of Ctgf and Vegf in sutures 3 hours after loading. The tensile force-induced Vegf expression in sutures was inhibited by the administration of CTGF-neutralizing antibody. The administration of CTGF-neutralizing antibody also inhibited sutural bone formation induced by tensile force. Moreover, we have cultured primary suture-derived cells to analyze CTGF function in vitro. Our findings indicate that CTGF is an essential factor to regulate biological response of sutures to tensile force.

Research Products

• [Journal Article] In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force (2016)
  • Author(s): Takeshita N, Hasegawa M, Sasaki K, Seki D, Seiryu M, Miyashita S, Takano I, Oyanagi T, Miyajima Y, Takano-Yamamoto T
  • Journal Title: J Bone Miner Metab Volume: 印刷中 Issue: 1 Pages: 40-51
  • DOI: 10.1007/s00774-016-0737-z
  • Peer Reviewed / Open Access
• [Journal Article] In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force (2016)
  • Author(s): Nobuo Takeshita, Masakazu Hasegawa, Kiyo Sasaki, Daisuke Seki, Masahiro Seiryu, Shunro Miyashita, Ikuko Takano, Toshihito Oyanagi, Yuki Miyajima, Teruko Takano-Yamamoto
  • Journal Title: J Bone Miner Metab Volume: in press
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Differentiation of odontoblast-like cells from mouse induced pluripotent stem cells by Pax9 and Bmp4 transfection (2015)
  • Author(s): Seki D, Takeshita N, Oyanagi T, Sasaki S, Takano I, Hasegawa M, Takano-Yamamoto T
  • Journal Title: Stem Cells Transl Med Volume: 4(9) Issue: 9 Pages: 993-997
  • DOI: 10.5966/sctm.2014-0292
  • Peer Reviewed / Open Access
• [Journal Article] Compressive force-produced CCN2 induces osteocyte apoptosis through ERK1/2 pathway (2014)
  • Author(s): K Hoshi, H Kawaki, I Takahashi, N Takeshita, M Seiryu, S A Murshid, T Masuda, T Anada, R Kato, H Kitaura, O Suzuki, T Takano-Yamamoto
  • Journal Title: J Bone Miner Res Volume: 29 Issue: 5 Pages: 1244-1257
  • DOI: 10.1002/jbmr.2115
  • NAID: 130004695790
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] CCN2/CTGFは牽引力が負荷された頭蓋縫合における骨および血管の形成を制御する (2016)
  • Author(s): 竹下信郎、佐々木紀代、関大輔、清流正弘、宮下俊郎、高野郁子、大柳俊仁、長谷川正和、山本照子
  • Organizer: 第７５回日本矯正歯科学会大会
  • Place of Presentation: 徳島
  • Year and Date: 2016-11-07
• [Presentation] CCN2/CTGFは牽引力が負荷された頭蓋縫合における血管および骨の形成を制御する (2016)
  • Author(s): 竹下信郎、佐々木紀代、関大輔、宮下俊郎、高野郁子、大柳俊仁、山本照子
  • Organizer: 第３４回日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-20
• [Presentation] IGF1による再生歯の形態制御とそのメカニズムの解析 (2016)
  • Author(s): 大柳俊仁、竹下信郎、関大輔、原真美子、池田悦子、高野郁子、清流正弘、吉田倫子、山本照子
  • Organizer: 第３４日本骨代謝学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2016-07-20
• [Presentation] 機械的刺激が促す骨形成過程における前駆骨芽細胞凝集へのCCN2/CTGFの影響 (2016)
  • Author(s): 竹下信郎、関大輔、清流正弘、木村晴地、高野郁子、大柳俊仁、吉田倫子、長谷川正和、山本照子
  • Organizer: 第８回日本CCNファミリー研究会
  • Place of Presentation: 岡山
• [Presentation] CCN2/CTGFはin vivoの機械的刺激に対する初期反応において縫合細胞の血管内皮細胞分化と骨細胞のアポトーシスを誘導する (2015)
  • Author(s): 竹下信郎、佐々木紀代、星健治、川木晴美、長谷川正和、山本照子
  • Organizer: 第７回CCNファミリー研究会
  • Place of Presentation: 岡山
  • Year and Date: 2015-08-29
• [Presentation] 牽引力に対する頭蓋縫合の初期反応における血管形成の分子的根拠と制御機構のin vivo解析 (2015)
  • Author(s): 竹下信郎、佐々木紀代、関大輔、宮下俊郎、高野郁子、大柳俊仁、長谷川正和、山本照子
  • Organizer: 第33回日本骨代謝学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2015-07-23
• [Presentation] 牽引力により誘導される頭蓋縫合における血管形成の分子制御機構の解析 (2014)
  • Author(s): 竹下信郎、長谷川正和、佐々木紀代、関大輔、宮下俊郎、高野郁子、大柳俊仁、宮島悠旗、山本照子
  • Organizer: 第７３回日本矯正歯科学会大会
  • Place of Presentation: 千葉
  • Year and Date: 2014-10-20 – 2014-10-22
• [Presentation] Tensile force induces vascular formation during the early biomechanical response of cranial sutures via ROCK2, CTGF, and ERK1/2 dependent mechanisms (2014)
  • Author(s): Nobuo Takeshita, Masakazu Hasegawa, Kiyo Sasaki, Daisuke Seki, Shunro Miyashita, Ikuko Takano, Yuki Miyajima, Teruko Takano-Yamamoto
  • Organizer: ASBMR 2014 Annual Meeting
  • Place of Presentation: Houston, Texas, USA
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] Tensile force induces vascular formation during the early biomechanical response of cranial sutures via ROCK2, CTGF, and ERK1/2 dependent mechanisms (2014)
  • Author(s): Nobuo Takeshita, Masakazu Hasegawa, Kiyo Sasaki, Daisuke Seki, Shunro Miyashita, Ikuko Takano, Yuki Miyajima, Teruko Takano-Yamamoto
  • Organizer: 9th International Workshop on Biomaterials in Interface Science
  • Place of Presentation: Zao, Miyagi
  • Year and Date: 2014-08-26 – 2014-08-27