Development of poiodontal regenerative medicine that based on molecular mechanism of cementogenesis.

• Project/Area Number: 15390580
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Conservative dentistry
• Research Institution: Kanagawa Dental College
• Principal Investigator: SAITO Masahiro Kanagawa Dental College, Dentistry, Lecturer, 歯学部, 講師 (40215562)
• Co-Investigator(Kenkyū-buntansha): TERANAKA Toshio Kanagawa Dental College, Dentistry, Professor, 歯学部, 教授 (60104460) ; KINOSHITA Yukihiko Kanagawa Dental College, Institute for Frontier Oral Science, Professor, 高次口腔科学研究所, 教授 (70084770) ; KIYONO Tohru National Cancer Center Research, Virology Division, Institute, Director, 研究所, 部長 (10186356) ; KIYONO Hidemitsu Osaka University, Graduate School of Dentistry, Associate Professor, 大学院・歯学研究科, 助教授 (70271210)
• Project Period (FY): 2003 – 2004
• Project Status: Completed (Fiscal Year 2004)
• Budget Amount: ¥14,600,000 (Direct Cost: ¥14,600,000); Fiscal Year 2004: ¥4,000,000 (Direct Cost: ¥4,000,000); Fiscal Year 2003: ¥10,600,000 (Direct Cost: ¥10,600,000)
• Keywords: Dental follicle / Extracellular matrix / Oxytalan fiber / tooth germ / Development / periodontium / Regeneration / Periodontal ligament / セメント質 / 移植実験 / 細胞分化 / モノクロナール抗体 / 歯周病

Research Abstract

Dental follicle is originated from cranial facial neural crest and it is believed to contain of progenitors for cementoblasts, periodontal ligament cells and osteoblasts. To analyze the differentiation potential of dental follicle, tooth root dentin with cementum and dental follicle are removed from developing tooth germ to be transplanted into the subcutaneous tissue of severe combined immunodeficiency(SCID) mice. After four-week transplantation, extensive amount of cementum matrix was formed between root dentin and dental follicle in the transplant. The newly formed cementum was became almost 20 folds ticker than the previously deposited cementum on root surface, and it was strongly positive for anti-cementum derived attachment protein monoclonal antibody. These results indicated that the cementoblast progenitors were presented in dental follicle, and they are able to differentiate into cementoblast on root surface. Transplantation study of the dental follicle provides a useful model for investigating molecular mechanisms of cementogenesis.
On the other hand, novel extracellular matrices have been identified by transcriptome analysis. Among these, a novel extracellulra matrix(ECM) that expressed in tendinous tissue was found to be expressed in the mice periodontal ligament. Immunohictochemical analysis showed that novel ECM found to form microfibril-like structure which is resembled with oxytalan fiber in the periodontal ligament. Aldehyde fuchusin staining analysis demonstrated that distribution of oxytalan fiber was agreement with those of novel ECM. These findings suggested that novel ECM is a new component that consist oxytalan fiber, and may use as a candidate molecule for the regenerative medicine of periodontal disease.

Research Products

• [Journal Article] Immortalization of cementoblast progenitor cells with Bmi-1 and TERT. (2005)
  • Author(s): M.Saito et al.
  • Journal Title: J Bone Miner Res 20・1 Pages: 50-57
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Alveolar Bone Marrow as a Cell Source for Regenerative Medicine : Differences between Alveolar and Iliac Bone Marrow Stromal Cells. (2005)
  • Author(s): T.Matsubara et al.
  • Journal Title: J Bone Miner Res 20・1 Pages: 399-409
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Molecular mechanisms of Periodontal development, and its prospect of regenerative medicine for periodontium. (2005)
  • Author(s): M.Saito, A.Tsunoda, T.Yokoi, S.Hattori, T.Tsubakimoto, E.Nishida, K.Kousaka, M.Toyoda, S.Sato, T.Noguchi, T.Teranaka.
  • Journal Title: Bulletin of Kanagawa dental college Vol.33(1) Pages: 31-35
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Immortalization of cementoblast progenitor cells with Bmi-1 and TERT. (2005)
  • Author(s): M.Saito, K.Handa, T.Kiyono, S.Hattori, T.Yokoi, T.Tsubakimoto, H.Harada, T.Noguchi, M.Toyoda, S.Sato, T.Teranaka
  • Journal Title: J Bone Miner Res 20(1) Pages: 50-57
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Alveolar Bone Marrow as a Cell Source for Regenerative Medicine : Differences between Alveolar and Iliac Bone Marrow Stromal Cells. (2005)
  • Author(s): T.Matsubara K.Suardita, M.Ishii, M.Sugiyama, A.Igarashi, R.Oda, M.Nishimura, Saito M, K.Nakagawa, K.Yamanaka, K.Miyazaki, M.Shimizu, K.Tsuji, K.Nakamura, Y.Kato
  • Journal Title: J Bone Miner Res 20(3) Pages: 399-409
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of a novel telomerase repressor by virtue of its interaction with the human papillomavirus type-16 E6/E6-AP complex. (2004)
  • Author(s): L.Gewin, et al.
  • Journal Title: Genes Dev 18 Pages: 2269-2282
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Ceramide triggers caspase activation during gamma-radiation-induced apoptosis of human glioma cells lacking functional p53. (2004)
  • Author(s): S.Hara
  • Journal Title: Oncol Rep 12 Pages: 119-123
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Production of prostaglandin E2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells. (2004)
  • Author(s): A.Kawabe
  • Journal Title: Life Sci 75 Pages: 21-34
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. (2004)
  • Author(s): N.Sugimoto
  • Journal Title: J Biol Chem 279 Pages: 19691-19697
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification and isolation of a cementoblast progenitor for periodontal regenerative therapy. (2004)
  • Author(s): M.Saito, S.Hattori, A.Tsunoda, T.Tsubakimoto, M.Toyoda S.Sato, T.Teranaka
  • Journal Title: Bull.Kanagawa Dent.Col. 32(1) Pages: 53-56
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterization of Dental Epithelial Progenitor Cells Derived from Cervical-loop Epithelium in a Rat Lower Incisor. (2004)
  • Author(s): S Kawano, M Saito, K Handa, T Morotomi, T Toyono, Y Seta, N Nakamura, T Uchida, K Toyoshima, M Ohishi, H Harada
  • Journal Title: J Dent Res. 83(2) Pages: 129-133
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of a novel telomerase repressor by virtue of its interaction with the human papillomavirus type-16 E6/E6-AP complex. (2004)
  • Author(s): Gewin, L., Myers, H., Kiyono, T., Galloway D.A.
  • Journal Title: Genes Dev. 18 Pages: 2269-2282
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Ceramide triggers caspase activation during gamma-radiation-induced apoptosis of human glioma cells lacking functional p53. (2004)
  • Author(s): Hara S, Nakashima S, Kiyono T, Sawada M, Yoshimura S, Iwama T, Sakai N.
  • Journal Title: Oncol Rep. 12 Pages: 119-123
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells. (2004)
  • Author(s): Kawabe, A., Shimada, Y., Soma, T., Maeda, M., Itami, A., Kaganoi, J., Kiyono, T., Imamura, M.
  • Journal Title: Life Sci 75 Pages: 21-34
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of a novel human gene, hWAPL, is associated with cervical carcinogenesis and tumor progression. (2004)
  • Author(s): Oikawa, K., Ohbayashi, T., Kiyono, T., Nishi, H., Isaka, K., Umezawa, A., Kuroda, M., Mukai, K.
  • Journal Title: Cancer Res. 64 Pages: 3545-3549
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Cdt1 phosphorylation by cyclin A-dependent kinases negatively regulates its function without affecting geminin binding. (2004)
  • Author(s): Sugimoto N, Tatsumi Y, Tsurumi T, Matsukage A, Kiyono T., Nishitani H, Fujita M.
  • Journal Title: J Biol Chem 279 Pages: 19691-19697
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] p53-independent ceramide formation in human glioma cells during γ-radiation-induced apoptosis. (2004)
  • Author(s): Hara, S., Nakashima, S., Kiyono, T., Sawada, M., Yoshimura, S., Yamada, J., Iwama, T., Banno, Y., Shinoda, J., Sakai, N.
  • Journal Title: Cell Death Differ. 11 Pages: 853-861
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Can the life-span of human marrow stromal cells be prolonged by bmi-1,E6,E7,and/or telomerase without affecting cardiomyogenic differentiation? (2004)
  • Author(s): Takeda, Y., Mori, T.Imabayashi, H, Kiyono, T., Gojo, S., Miyoshi, S., Ita, M., Segawa, K., Ogawa, S., Sakamoto, M., Nakamura, S., Umezawa, A.
  • Journal Title: J.Gene Med. 6 Pages: 833-845
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular mechanisms of TNF-α-Induced ceramide formation in human glioma cells. (2004)
  • Author(s): Sawada, M., Kiyono, T., Nakashima, S., Shinoda, J., Naganawa, T., Hara, S., Iwama, T., Sakai, N.
  • Journal Title: Cell Death Differ. 11 Pages: 997-1008
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Inhibition of S-phase cyclin-dependent kinase activity blocks expression of Epstein-Barr virus immediate-early and early genes, preventing viral lytic replication. (2004)
  • Author(s): Kudoh, A., Daikoku, T., Sugaya, Y., Isomura, H., Fujita, M., Kiyono, T., Nishiyama, Y., Tsurumi T.
  • Journal Title: J.Virol. 78 Pages: 104-115
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Production of prostaglandinE2 via bile acid is enhanced by trypsin and acid in normal human esophageal epithelial cells. (2004)
  • Author(s): A.Kawabe
  • Journal Title: Life Sci 75 Pages: 21-34
• [Journal Article] Cultured Dental Follicle Cells are able to Produce Cementum Matrix In Vivo (2003)
  • Author(s): M.Saito, K.Handa, M.Yamauchi, T.Kiyono, S.Sato S.Narayanan, T.Ternaka
  • Journal Title: Archives of Comparative Biology of Tooth Enamel 8 Pages: 95-97
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Experimental Model for Cementogenesis using Dental Follicle (2003)
  • Author(s): K.Handa, M.Saito, A.Tsunoda, S.Hattori, M.Yamauchi, M.Toyoda, S.Sato, T.Teranaka
  • Journal Title: The Bulletin of Kanagawa dental college Vol.31 Pages: 74-76
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Redifferentiation of dedifferentiated chondrocytes and chondrogenesis of human bone marrow stromal cells via chondrpsphere formation with expression profiling by large-scale cDNA analysis. (2003)
  • Author(s): Imabayashi, H., Mori, T., Gojo, S., Kiyono, T., Sugiyama, T., Irie, R., Isogai, T., Hata, J., Toyama, Y., Umezawa, A.
  • Journal Title: Exp.Cell Res. 288 Pages: 35-50
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Atorvastatin inhibits expression of minichromosome maintenance proteins in vascular muscle cells. (2003)
  • Author(s): Bruemmer, D, Yin, F., Liu, J., Kiyono, T., Fleck, E., van Herle, A., Graf, K, Law, R.E.
  • Journal Title: Europ.J.Pharmacol 462 Pages: 15-23
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Filament formation of MSF-A, a mammalian septin, in mammary HMEC cells depends on interactions with microtubules. (2003)
  • Author(s): Nagata KI, Kawajiri A, Matsui S, Takagishi M, Shiromizu T, Saitoh N, Izawa I, Kiyono T, Itoh TJ, Hotani H, Inagaki M.
  • Journal Title: J.Biol.Chem. 278 Pages: 18538-18543
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Rapamycin inhibits E2F-dependent expression of minichromosome maintenance proteins in vascular smooth muscle cells. (2003)
  • Author(s): Bruemmer D, Yin F, Liu J, Kiyono T, Fleck E, Van Herle AJ, Law RE.
  • Journal Title: Biochem.Biophys.Res.Commun. 303 Pages: 251-258
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Peroxisome proliferator-activated receptor inhibits expression of minichromosome maintenance proteins in vascular smooth muscle cells. (2003)
  • Author(s): Bruemmer D, Yin F, Liu J, Berger JP, Kiyono T, Chen J, Fleck E, Van Herle AJ, Forman BM, Law RE.
  • Journal Title: Mol.Endoclinol. 17 Pages: 1005-1018
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Reactivation of lytic replication from Epstein-Barr virus latently infected B-cells occurs with high S-phase CDK activity while inhibiting celluar DNA replication. (2003)
  • Author(s): Kudoh, A., Fujita, M., Kiyono, T., Kuzushima, K., Sugaya, Y., Izuta, S., Nishiyama, Y., Tsurumi, T.
  • Journal Title: J.Virol. 77 Pages: 851-861
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Establishment of latrunculin-A-resistance in HeLa cells by expression of R183A D184A mutant β-actin. (2003)
  • Author(s): Fujita, M., Ichinose, S., Kiyono, T., Tsurumi, T., Omori, A.
  • Journal Title: Oncogene 22 Pages: 627-631
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Saito.M et al.: "Cultured Dental Follicle Cells are able to Produce Cementum Matrix In vivo."Archives of Comparative Biology of Tooth Enamel. 8. 95-97 (2003)
• [Publications] Saito.M et al.: "Identification and isolation of a cementoblast progenitor for periodontal regenerative therapy"Bull.Of Kanagawa Dental College. In press. (2003)
• [Publications] S.Kawano: "Characterization of Dental Epithelial Progenitor Cells Derived from Cervical-loop"Journal of Dental Resrch. 83(2). 129-133 (2004)
• [Publications] Fujita M: "Establishment of latrunculin-A-resistance in HeLa cells by expression of R183A D184A mutant β-actin."Oncogene. 22. 627-631 (2003)
• [Publications] Nagata K: "Filament formation of MSF-A, a mammalian septin, in mammary HMEC cells depends on interactions with microtubules."J.Biol.Chem.. 278. 18538-1854 (2003)
• [Publications] Bruemmer D: "Rapamycin inhibits E2F-dependent expression of minichromosome maintenance proteins in vascular smooth muscle cells."Biochem.Biophys.Res.Commun.. 303. 251-258 (2003)