Analysis of mechanism of regulation of CTGF/CCN2 by RUNX2 in tooth formation

• Project/Area Number: 18K09743
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 57060:Surgical dentistry-related
• Research Institution: Okayama University
• Principal Investigator: MORITANI NORIFUMI 岡山大学, 医歯薬学域, 講師 (60467751)
• Co-Investigator(Kenkyū-buntansha): 滝川 正春 岡山大学, 医歯薬学域, 教授 (20112063) ; 久保田 聡 岡山大学, 医歯薬学域, 教授 (90221936) ; 高畠 清文 岡山大学, 医歯薬学域, 助教 (70736537) ; 星島 光博 岡山大学, 医歯薬学域, 助教 (30736567) ; 松村 達志 和歌山県立医科大学, 医学部, 教授 (70432648)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: CTGF/CCN2 / RUNX2 / tooth formation / 歯の形成

Outline of Final Research Achievements

Analysis of teeth extract from subjects with cleidocranial dysplasia and normal subjects revealed changes in protein localization of RUNX family transcription factor 2 (RUNX2) and connective tissue growth factor (CTGF/CCN2). Positive correlations were evident between RUNX2 and CTGF/CCN2 gene expression promotion and suppression in Saos-2 cells. Several RUNX2 protein candidate regions were identified that altered CTGF/CCN2 expression in Cos-7 cells. The findings indicate that the structure of RUNX2 protein changes depending on the mutation site of the RUNX2 gene, and that the CTGF/CCN2 expression changes accordingly. These changes result in an altered phenotype of cleidocranial dysplasia involved in tooth eruption.

Academic Significance and Societal Importance of the Research Achievements

歯の形成において重要なRUNX2がCTGF/CCN2の発現を調節し，その調節機構を解析したことによって，歯の形成を指揮する重要なメカニズムの一端を解明する手がかりとなる結果を得た．これらの結果は，歯の再生医療を樹立するための基盤となり，また，鎖骨頭蓋異形成症患者においては，RUNX2遺伝子変異箇所の違いに対して，歯科的なオーダーメイド治療を行うための一助となる成果となったではないかと考えている．

Research Products

• [Journal Article] Selective Agonists of Nuclear Retinoic Acid Receptor Gamma Inhibit Growth of HCS-2/8 Chondrosarcoma Cells (2019)
  • Author(s): W. P. Shield, 3rd, A. Cellini, H. Tian, K. Wilson, Y. Dan, J. M. Abzug, S. Garcia, N. Moritani, I. Alferiev, M. Chorny, M. Takigawa, V. Y. Ng, M. Iwamoto.M. Enomoto-Iwamoto.
  • Journal Title: J Orthop Res Volume: - Issue: 5 Pages: 1045-1051
  • DOI: 10.1002/jor.24555
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intermittent parathyroid hormone 1?34 induces oxidation and deterioration of mineral and collagen quality in newly formed mandibular bone (2019)
  • Author(s): Yoshioka Yohsuke、Yamachika Eiki、Nakanishi Makoto、Ninomiya Tadashi、Akashi Sho、Kondo Sei、Moritani Norifumi、Kobayashi Yasuhiro、Fujii Tatsuo、Iida Seiji
  • Journal Title: Scientific Reports Volume: 9 Issue: 1 Pages: 8041-8041
  • DOI: 10.1038/s41598-019-44389-8
  • NAID: 120006777525
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] New Functions of Classical Compounds against Orofacial Inflammatory Lesions (2018)
  • Author(s): N. Moritani, ES. Hara, S. Kubota
  • Journal Title: Medicines (Basel) Volume: 5 Issue: 4 Pages: 118-118
  • DOI: 10.3390/medicines5040118
  • Peer Reviewed / Open Access
• [Presentation] Localization of RUNX2 and CCN2 proteins in the supernumerary tooth of a cleidocranial patient (2018)
  • Author(s): N. Moritani, K. Takabatake, S. Kubota, Y. Yoshioka, M. Hoshijima, Y Matsui, E. Yamachika, S. Iida.
  • Organizer: The 13nd Asian Congress on Oral & Maxillofacial Surgery (ACOMS)
  • Int'l Joint Research