Evaluation of a mouse odontoma model and elucidation of the developmental mechanisms of odontoma

• Project/Area Number: 15390572
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Osaka Dental University
• Principal Investigator: NOZAKI Tadashige Osaka Dental University, Assistant Professor, 歯学部, 講師 (90281683)
• Co-Investigator(Kenkyū-buntansha): OHURA Kiyoshi Osaka Dental University, Professor, 歯学部, 教授 (20131378)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥11,100,000 (Direct Cost: ¥11,100,000); Fiscal Year 2005: ¥2,600,000 (Direct Cost: ¥2,600,000); Fiscal Year 2004: ¥4,700,000 (Direct Cost: ¥4,700,000); Fiscal Year 2003: ¥3,800,000 (Direct Cost: ¥3,800,000)
• Keywords: odontoma / differentiation / odontoblast / ameloblast / ghost cell / PARP1 / 遺伝子操作 / odontoma / Parp-1 / ノックアウトマウス

Research Abstract

Poly (ADP-ribose) polymerase (Parp1) is known to play roles in cell death and cell differentiation through transcriptional control. In the present study, decalcified mandibles, including the incisors, from Parp1-/- and wild-type Parp1^<+/+> mice with a genetic background of ICR/129Sv maintained on a basal diet for 2 years were subjected to histological analyses. A total of 10 samples from male Parp1^<-/-> mice and 13 samples from male Parp1^<+/+> mice were analyzed. In all samples from the Parp1^<-/-> mice, the dentin showed remarkable proliferation and irregularly lined odontoblasts were observed on the inside of the dental pulp cavity. In contrast, the odontoblasts in the samples from the Parp1^<+/+> mice were regularly lined up on the side of the dental pulp and no abnormalities of the enamel were observed. To elucidate the involvement of PARP1 in the development of human odontoma, samples obtained from 7 complex type and 6 compound type human odontoma cases were analyzed immunohist ochemically for their expressions of PARP1. The results revealed that PARP1 was expressed in tooth germ-like tissue, reduced enamel epithelium, immature dentin and immature enamel in the odontomas. Moreover, its expression was detected in odontoblasts and the epithelial component corresponding to ameloblasts. These findings indicate that PARP1 contributes to the differentiation of the cells that constitute odontomas. In addition, PARP1 was expressed in the cytoplasm of ghost cells that did not possess a nucleus. The cytoplasm of these ghost cells was also strongly immunostained by the M30CytoDEATH antibody raised against the cleavage site of cytokeratin 18 produced during the process of apoptosis. Since ghost cells are considered to represent a type of degenerative cells that accumulate hard keratins, and some early apoptosis events seem to have occurred, these observations indicate that PARP1 expression in ghost cells undergoing apoptosis contributed to the formation of these cells in odontomas.

Research Products

• [Journal Article] Expression of PARP1 in odontoma (2006)
  • Author(s): Nozaki, T.
  • Journal Title: Journal of Meikai University School of Dentistry 35(1)(in press)
  • NAID: 40015368595
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv nice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky sdducts (2006)
  • Author(s): Gunji, A.
  • Journal Title: Cancer Letters (in press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Expression of PARP1 in odontoma (2006)
  • Author(s): Nozaki, T., Watanabe, M., Morita, J., Ohura, K., Kusama, K.
  • Journal Title: J.Meikai Univ.Sch. of Dent. 35(1)(in press)
  • NAID: 40015368595
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv mice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky adducts (2006)
  • Author(s): Gunji, A., Uemura, A., Tsutsumi, M., Nozaki, T., Kusuoka, O., Omura, K., Suzuki, H., Nakagama, H., Sugimura, T., Masutani, M.
  • Journal Title: Cancer Lett. (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Expression of PARP1 in odontoma (2006)
  • Author(s): Nozaki, T. et al.
  • Journal Title: Journal of Meikai University School of Dentistry 35(1)(in press)
  • NAID: 40015368595
• [Journal Article] Parp-1 deficiency does not increase the frequency of tumors in the oral cavity and esophagus of ICR/129Sv mice by 4-nitroquinoline 1-oxide, a carcinogen producing bulky adducts (2006)
  • Author(s): Gunji, A., et al.
  • Journal Title: Cancer Lett. (in press)
• [Journal Article] Differentiation of rat dental pulp-derived cells into an osteoblastic lineage (2005)
  • Author(s): Nozaki, T.
  • Journal Title: Oral Science international 2(2) Pages: 118-125
  • NAID: 10020401693
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Differentiation of rat dental pulp-derived cells into an osteoblastic lineage (2005)
  • Author(s): Nozaki, T., Takeyasu, M., Hirao, A., Shinohara, M., Daito, M., Ohura, K.
  • Journal Title: Oral Sci.Int. 2(2) Pages: 118-125
  • NAID: 10020401693
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Differentiation of rat dental pulp-derived cells into an osteoblastic lineage (2005)
  • Author(s): Nozaki, T. et al.
  • Journal Title: Oral Sci.Int. 2(2) Pages: 118-125
  • NAID: 10020401693
• [Journal Article] In vitro osteogenic differentiation potential of dental pulp stem cells (2004)
  • Author(s): Takeyasu, M.
  • Journal Title: Journal of Oral Tissue Engineering 2(1) Pages: 25-30
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Poly(ADP-ribose) polymerase-1 gene in human tumor cell lines : Its expression and structural alteration (2004)
  • Author(s): Masutani, M.
  • Journal Title: Proceeding of the Japan Academy Ser.B80 Pages: 114-118
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] In vitro osteogenic differentiation potential of dental pulp stem cells (2004)
  • Author(s): Takeyasu, M., Nozaki, T., Watanabe, M., Shinohara, M., Morita, J., Hidaka, A., Iwamoto, K., Takahashi, T., Nagata, S., Daito M., Ohura, K.
  • Journal Title: J.Oral Tissue Engin. 2(1) Pages: 25-30
  • NAID: 110006164156
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Poly(ADP-ribose) polymerase-1 gene in human tumor cell lines : Its expression and structural alteration (2004)
  • Author(s): Masutani, M., Nozaki, T., Sasaki, H., Yamada, T., Kohno, T., Shimizu, K., Gotoh, M., Shiraishi, M., Yokota, J., Hirohashi, S., Nakagama, H., Sugimura, T.
  • Journal Title: Proc.Japan Acad. Ser.B80 Pages: 114-118
  • NAID: 130000093766
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] In vitro Osteogenic Differentiation Potential of Dental Pulp Stem Cells (2004)
  • Author(s): M.Takeyasu et al.
  • Journal Title: J.Oral Tissue Engin. 2(1) Pages: 25-30
• [Journal Article] Parp-1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane (2003)
  • Author(s): Nozaki, T.
  • Journal Title: Cancer Science 94(6) Pages: 497-500
  • NAID: 10011689259
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Parp-1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane (2003)
  • Author(s): Nozaki, T., Fujihara, H., Watanabe, M., Tsutsumi, M., Nakamoto, K., Kusuoka, O., Kamada, N., Suzuki, H., Nakagama, H., Sugimura, T., Masutani, M.
  • Journal Title: Cancer Sci. 94(6) Pages: 497-500
  • NAID: 10011689259
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Nozaki T, et al.: "Parp-1 deficiency implicated in colon and liver tumorigenesis induced by azoxymethane"Cancer Sci.. 94. 497-500 (2003)
• [Publications] Hemberger M., Nozaki T., et al.: "Parpi-deficiency induces differentiation of ES cells into trophoblast derivatives"Dev Biol.. 257. 371-381 (2003)
• [Publications] Hemberger M., Nozaki T., et al.: "Differential expression of angiogenic and vasodilatory factors by invasive trophoblast giant cells depending on depth of invasion"Dev.Dyn.. 227. 185-191 (2003)
• [Publications] Torii N., Nozaki T., et al.: "Spontaneous mutations in the Helicobacter pylori rpsL gene"Mutat.Res.. 535. 141-145 (2003)
• [Publications] Shibata A., Masutani M., Nozaki T., et al.: "Improvement of the Spi-assay for mutations in gpt delta mice by including magnesium ions during plaque formation"Environ.Mol.Mutagen.. 41. 370-372 (2003)