Elucidation of transcriptional regulatory mechanisms in dental pulp stem cell differentiation

• Project/Area Number: 18K09638
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57040:Regenerative dentistry and dental engineering-related
• Research Institution: Hiroshima University
• Principal Investigator: Fujimoto Katsumi 広島大学, 医系科学研究科(歯), 助教 (40294566)
• Co-Investigator(Kenkyū-buntansha): 佐藤 冬樹 静岡県立静岡がんセンター(研究所), その他部局等, 研究員 (60400131) ; 金輪 真佐美 (福永真佐美) 広島大学, 自然科学研究支援開発センター, 助教 (00284208)
• Project Period (FY): 2018-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
• Keywords: 歯髄 / 幹細胞 / 転写因子 / 細胞分化 / 歯髄幹細胞 / MSX1 / MSX2

Outline of Final Research Achievements

It was suggested that MSX1 and MSX2 function as odontoblast/osteoblast differentiation-promoting and adipocyte differentiation-inhibitory factors in dental pulp stem cells. In addition, in order to elucidate the mechanism, we comprehensively analyzed a group of genes that act downstream of MSX1. Inflammatory cytokine TNF-α, which is secreted by tooth injury stimulation, induced MSX1 expression, but did not affect MSX expression, in dental pulp stem cells. Immunohistochemical analyses demonstrated that MSX1 and MSX2 proteins were highly expressed in the nuclei of odontoblasts in roots where dentin formation was active.

Academic Significance and Societal Importance of the Research Achievements

近年、幹細胞を用いた再生医療が注目されている。その中で、歯髄再生の元になる体性幹細胞である歯髄幹細胞は、その優れた分化能のため再生医療の細胞源として様々な組織（歯髄、骨、神経、血管等）での利用が期待されている。歯髄幹細胞は他の体性幹細胞と比べ象牙芽細胞や神経細胞への分化能が高いなどの特徴を持つが、その分子メカニズムは不明である。転写因子による分化制御メカニズムの解明は、歯髄幹細胞の特徴を明らかにするために重要である。本研究の成果は、将来的に歯髄幹細胞を用いた細胞治療の効果的な利用に役立つと期待される。

Research Products

• [Journal Article] Study of Alveolar Bone Remodeling Using Deciduous Tooth Stem Cells and Hydroxyapatite by Vascular Endothelial Growth Factor Enhancement and Inhibition of Matrix Metalloproteinase-8 Expression in vivo (2022)
  • Author(s): Saskianti Tania、Nugraha Alexander Patera、Prahasanti Chiquita、Ernawati Diah Savitri、Tanimoto Kotaro、Riawan Wibi、Kanawa Masami、Kawamoto Takeshi、Fujimoto Katsumi
  • Journal Title: Clinical, Cosmetic and Investigational Dentistry Volume: Volume 14 Pages: 71-78
  • DOI: 10.2147/ccide.s354153
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] BHLHE41/DEC2 Expression Induces Autophagic Cell Death in Lung Cancer Cells and Is Associated with Favorable Prognosis for Patients with Lung Adenocarcinoma. (2021)
  • Author(s): Toshiyuki Nagata, Kentaro Minami, Masatatsu Yamamoto, Tsubasa Hiraki, Masashi Idogawa, Katsumi Fujimoto, Shun Kageyama, Kazuhiro Tabata, Kohichi Kawahara, Kazuhiro Ueda, Ryuji Ikeda, Yukio Kato, Masaaki Komatsu, Akihide Tanimoto, Tatsuhiko Furukawa, Masami Sato
  • Journal Title: International journal of molecular sciences Volume: 22 Issue: 21 Pages: 11509-11509
  • DOI: 10.3390/ijms222111509
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] The Identification of Marker Genes for Predicting the Osteogenic Differentiation Potential of Mesenchymal Stromal Cells (2021)
  • Author(s): Kanawa Masami、Igarashi Akira、Fujimoto Katsumi、Saskianti Tania、Nakashima Ayumu、Higashi Yukihito、Kurihara Hidemi、Kato Yukio、Kawamoto Takeshi
  • Journal Title: Current Issues in Molecular Biology Volume: 43 Issue: 3 Pages: 2157-2166
  • DOI: 10.3390/cimb43030150
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] CHRONO and DEC1/DEC2 compensate for lack of CRY1/CRY2 in expression of coherent circadian rhythm but not in generation of circadian oscillation in the neonatal mouse SCN. (2021)
  • Author(s): Ono D, Honma KI, Schmal C, Takumi T, Kawamoto T, Fujimoto K, Kato Y, Honma S.
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 19240-19240
  • DOI: 10.1038/s41598-021-98532-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] DEC1 regulates the rhythmic expression of PPARγ target genes involved in lipid metabolism in white adipose tissue (2020)
  • Author(s): Noshiro Mitsuhide、Kawamoto Takeshi、Nakashima Ayumu、Ozaki Noritsugu、Saeki Masayumi、Honda Kiyomasa、Fujimoto Katsumi、Kato Yukio
  • Journal Title: Genes to Cells Volume: 25 Issue: 4 Pages: 232-241
  • DOI: 10.1111/gtc.12752
  • Peer Reviewed
• [Journal Article] Potential Marker Genes for Predicting Adipogenic Differentiation of Mesenchymal Stromal Cells (2019)
  • Author(s): Masami Kanawa, Akira Igarashi, Katsumi Fujimoto, Veronica Sainik Ronald, Yukihito Higashi, Hidemi Kurihara, Yukio Kato, Takeshi Kawamoto
  • Journal Title: Applied Sciences Volume: 9 Issue: 14 Pages: 1-9
  • DOI: 10.3390/app9142942
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Genetic Markers Can Predict Chondrogenic Differentiation Potential in Bone Marrow-Derived Mesenchymal Stromal Cells (2018)
  • Author(s): Kanawa M, Igarashi A, Fujimoto K, Higashi Y, Kurihara H, Sugiyama M, Saskianti T, Kato Y, Kawamoto T
  • Journal Title: Stem Cells International Volume: 10 Pages: 1-9
  • DOI: 10.1155/2018/9530932
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Deficiency of the basic helix-loop-helix transcription factor DEC1 prevents obesity induced by a high-fat diet in mice (2018)
  • Author(s): Noshiro Mitsuhide、Kawamoto Takeshi、Nakashima Ayumu、Ozaki Noritsugu、Ueno Toshinori、Saeki Masayumi、Honda Kiyomasa、Fujimoto Katsumi、Kato Yukio
  • Journal Title: Genes to Cells Volume: 23 Issue: 8 Pages: 658-669
  • DOI: 10.1111/gtc.12607
  • NAID: 120006979719
  • Peer Reviewed / Open Access
• [Journal Article] Characterization of human dental pulp cells grown in chemically defined serum-free medium (2018)
  • Author(s): Fujii S, Fujimoto K, Goto N, Abiko Y, Imaoka A, Shao J, Kitayama K, Kanawa M, Sosiawan A, Suardita K, Nishimura F, Kato Y
  • Journal Title: Biomed Rep Volume: 8(4) Pages: 350358-350358
  • DOI: 10.3892/br.2018.1066
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 骨髄由来間葉系幹細胞（MSC）の骨、軟骨、脂肪分化予知マーカー遺伝子の同定 (2023)
  • Author(s): 金輪真佐美, 五十嵐 晃, 藤本勝巳, Veronica Sainik Ronald, Tania Saskianti, 中島 歩, 東 幸仁, 栗原英見, 加藤幸夫, 河本 健
  • Organizer: 第22回日本再生医療学会総会
• [Presentation] Identification of Marker Genes for Predicting the Osteogenic Differentiation Potential of Mesenchymal Stromal Cells (2022)
  • Author(s): Masami Kanawa, Akira Igarashi, Katsumi Fujimoto, Tania Saskianti Ayumu Nakashima, Yukihito Higashi, Hidemi Kurihara, Yukio Kato, Takeshi Kawamoto
  • Organizer: 第45回日本分子生物学会年会
  • Int'l Joint Research
• [Presentation] 骨髄由来MSCの脂肪分化予知遺伝子マーカーの同定 (2020)
  • Author(s): 金輪真佐美、五十嵐晃、藤本勝巳、東幸仁、栗原英見、加藤幸夫、河本健
  • Organizer: 第43回日本分子生物学会
  • Int'l Joint Research
• [Presentation] 3D解析による骨髄由来間葉系幹細胞の軟骨分化予知遺伝子マーカーの研究 (2019)
  • Author(s): 金輪 真佐美、五十嵐 晃、藤本 勝巳、東 幸仁、栗原 英見、杉山 勝、加藤 幸夫、河本 健
  • Organizer: 第42回日本分子生物学会年会