Role of MSX1 in osteo/odontogenic differentiation of human dental pulp stem cells

• Project/Area Number: 15K20592
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Orthodontics/Pediatric dentistry
• Research Institution: Hiroshima University
• Principal Investigator: GOTO NORIKO 広島大学, 病院(歯), 歯科診療医 (10735137)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: MSX1 / 歯髄幹細胞 / 骨分化 / SREBP2 / コレステロール合成 / アルカリフォスファターゼ / RUNX2 / siRNA / 象牙芽細胞分化 / DNAマイクロアレイ / 脂質代謝

Outline of Final Research Achievements

When human dental pulp stem cells were exposed to osteogenesis-induction medium, runt-related transcription factor-2 (RUNX2), bone morphogenetic protein-2 (BMP2), alkaline phosphatase (ALPL) mRNA levels, as well as alkaline phosphatase activity, increased on days 4-12 and thereafter the matrix was calcified on day 14. However, knockdown of MSX1 with small interfering RNA abolished the induction of the osteoblast-related gene expression, alkaline phosphatase activity and calcification. Interestingly, DNA microarray and PCR analyses revealed that MSX1 knockdown induced the sterol regulatory element-binding protein 2 (SREBP2) transcriptional factor and its downstream target genes in the cholesterol-synthesis pathway. Inhibition of cholesterol synthesis enhances osteoblast differentiation of various mesenchymal cells. Thus, MSX1 may downregulate the cholesterol synthesis-related genes to ensure osteoblast differentiation of human dental pulp stem cells.

Research Products

• [Journal Article] Role of MSX1 in osteogenic differentiation of human dental pulp stem cells (2016)
  • Author(s): Goto N, Fujimoto K, Fujii S, Ida-Yonemochi H, Ohshima H, Kawamoto T, Noshiro M, Shukunami C, Kozai K, Kato Y.
  • Journal Title: Stem cells international Volume: 2016 Issue: 1 Pages: 1-13
  • DOI: 10.1155/2016/8035759
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] DEC2 is a negative regulator for the proliferation and differentiation of chondrocyte lineage-committed mesenchymal stem cells (2016)
  • Author(s): Sasamoto, T., Fujimoto, K., Kanawa, M., Kimura, J., Takeuchi, J., Harada, N., Goto, N., Kawamoto, T., Noshiro, M., Suardita, K., Tanne, K., Kato, Y.
  • Journal Title: Int. J. Mol. Med Volume: 印刷中 Issue: 3 Pages: 876-884
  • DOI: 10.3892/ijmm.2016.2660
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] 当科にて長期的口腔管理を行ったDonohue症候群患児の１例 (2015)
  • Author(s): 五藤紀子，大原紫，新里法子，川越麻衣子，古庄寿子，光畑智恵子，高田隆，香西克之
  • Journal Title: 広島大学歯誌 Volume: 47(2) Pages: 163-169
  • Peer Reviewed
• [Journal Article] Characteristic expression of MSX1, MSX2, TBX2 and ENTPD1 in dental pulp cells (2015)
  • Author(s): Fujii, S. Fujimoto, K. Goto, N. Kanawa, M. Kawamoto, T. Pan, H. Srivatanakul, P. Rakdang, W. Pornprasitwech, J. Saskianti, T. Suardita, K. Nishimura, F. Kato, Y.
  • Journal Title: Biomed Rep. Volume: 3 Issue: 4 Pages: 566-572
  • DOI: 10.3892/br.2015.456
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] 1：歯髄幹細胞においてホメオボックス型転写因子MSX1はコレステロール合成関連遺伝子の発現を制御する。 (2015)
  • Author(s): 五藤紀子、藤本勝巳、藤井紗貴子、依田浩子、大島勇人、河本健、能城光秀、宿南知佐、香西克之、加藤幸夫
  • Organizer: 第38回日本分子生物学会年会第88回日本生化学会合同大会
  • Place of Presentation: 兵庫県神戸市
  • Year and Date: 2015-12-01
• [Presentation] 2：ホメオボックス型転写因子MSX1による歯髄幹細胞分化制御 (2015)
  • Author(s): 藤本勝巳、五藤紀子、河本健、能城光秀、宿南知佐、香西克之、加藤幸夫
  • Organizer: 第99回広島大学歯学会 併催 第54回広島県歯科医学会
  • Place of Presentation: 広島県広島市
  • Year and Date: 2015-11-08