Epigenetic regulation underlying bone and cartilage regenaration

• Project/Area Number: 25293401
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Dental engineering/Regenerative dentistry
• Research Institution: Osaka University
• Principal Investigator: Hata Kenji 大阪大学, 歯学研究科(研究院), 准教授 (80444496)
• Project Period (FY): 2013-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
• Keywords: 軟骨細胞 / エピジェネティクス / DNAメチル化 / エピジェネテック / 骨芽細胞

Outline of Final Research Achievements

Accumulating evidences demonstrated that epigenetic regulation play important roles in tissue regeneration including bone and cartilage regeneration. However, epigenetic regulatory mechanism underlying bone and cartilage development remains to be elusive. In this study, we established several cloning strategy to identify novel epigenetic factors controlling bone and cartilage development. We have identified Foxc1/Foxc2 and found that Foxc1/Foxc2 regulates Ihh-Gli2 signaling during endochondral bone development. We believe that these findings would contribute to the development of novel regenerative medicine for bone and cartilage.

Research Products

• [Journal Article] Syntaxin 4a regulates matrix vesicle-mediated bone matrix production by osteoblasts (2017)
  • Author(s): Kawai S*, Michikami I, Kitagaki J, Hata K, Kiyonari H, Abe T, Amano A, Wakisaka S
  • Journal Title: Journal of Bone and Mineral Research Volume: 32 Issue: 3 Pages: 440-448
  • DOI: 10.1002/jbmr.3056
  • Peer Reviewed
• [Journal Article] Acidic microenvironments induce lymphangiogenesis and IL-8 production via TRPV1 activation in human lymphatic endothelial cells (2016)
  • Author(s): Nakanshi M, Morita Y, Hata K, Muragaki Y
  • Journal Title: Exp Cell Res Volume: 345 Issue: 2 Pages: 180-189
  • DOI: 10.1016/j.yexcr.2016.06.006
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] 口腔疾患に対するPTHおよびBMPの臨床応用の可能性 (2016)
  • Author(s): 波多 賢二
  • Journal Title: Clinical Calcium Volume: 26(3) Pages: 126-133
• [Journal Article] Epigenetic regulation of chondrocyte differentiation (2015)
  • Author(s): Kenji Hata
  • Journal Title: Japanese Dental Science Review Volume: 51 Issue: 4 Pages: 105-113
  • DOI: 10.1016/j.jdsr.2015.05.001
  • NAID: 50009780249
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [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] 軟骨細胞分化のエピゲノム (2014)
  • Author(s): 波多 賢二
  • Journal Title: 腎と骨代謝 Volume: 27 Pages: 261-266
• [Journal Article] 軟骨細胞の分化制御 (2014)
  • Author(s): 波多賢二
  • Journal Title: 骨粗鬆症治療 Volume: 13 Pages: 173-176
• [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
• [Presentation] A transcription factor Zfhx4 functions as a transcriptional platform for Osterix during endochondral ossification (2015)
  • Author(s): Nakamura E, Hata K, Yoshida M, Murakami T, Takahata Y, Abe M, Wakisaka S, Yoneda T, Nishimura R.
  • Organizer: ASBMR annual meeting
  • Place of Presentation: Seattle, USA
  • Year and Date: 2015-10-09
  • Int'l Joint Research
• [Presentation] The transcription factor Foxc1 regulates chondrocyte hypertrophy in a synergistic cooperation with Runx2 (2014)
  • Author(s): Yoshida M, Hata K, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T
  • Organizer: 36th Annual meeting of The American Society for Bone and Mineral Research
  • Place of Presentation: Houston, Texas, USA
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] The novel transcription factor Zinc Finger Homeobox 4 (Zfhx4) is critical to late stage of endochondral ossification. (2014)
  • Author(s): Nakamura E, Hata K, Wakabayashi M, Yura Y, Yoneda T, Nishimura R.
  • Organizer: 36th Annual meeting of The American Society for Bone and Mineral Research
  • Place of Presentation: Houston, Texas, USA
  • Year and Date: 2014-09-12 – 2014-09-15
• [Presentation] The transcription factor zinc finger homeobox 4 (Zfhx4) plays a novel role in the regulation of endochondral ossification. (2014)
  • Author(s): Nakamura E, Hata K, Wakabayashi M, Yura Y, Yoneda T, Nishimura R.
  • Organizer: 24th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting
  • Place of Presentation: Qweenstown，NZ
  • Year and Date: 2014-09-07 – 2014-09-10
• [Presentation] The transcription factor Foxc1 controls endochondral ossification through the direct regulation of PTHrP and Cola10a1 expression under the partnership with Gli2 and Runx2 (2014)
  • Author(s): Yoshida M, Hata K, Iseki S, Takano-Yamamoto T, Nishimura R, Yoneda T.
  • Organizer: ECTS 2014
  • Place of Presentation: Prague, Czech Republic
  • Year and Date: 2014-05-17 – 2014-05-20
• [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，Robert H. Whitson，西村理行，米田俊之
  • Organizer: 第60回日本生化学会近畿支部例会
  • Place of Presentation: 大阪