Spontaneous Development of Dental Dysplasia in Aged Parp-1 Knockout Mice

Hisako Fujihara; Tadashige Nozaki; Masahiro Tsutsumi; Mayu Isumi; Shinji Shimoda; Yoshiki Hamada; Mitsuko Masutani

doi:10.3390/cells8101157

Spontaneous Development of Dental Dysplasia in Aged Parp-1 Knockout Mice

Cells. 2019 Sep 27;8(10):1157. doi: 10.3390/cells8101157.

Authors

Hisako Fujihara^{1

2}, Tadashige Nozaki^{3

4}, Masahiro Tsutsumi⁵, Mayu Isumi⁶, Shinji Shimoda⁷, Yoshiki Hamada⁸, Mitsuko Masutani^{9

10

11}

Affiliations

¹ Biochemistry Division, National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. fujihara-h@tsurumi-u.ac.jp.
² Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. fujihara-h@tsurumi-u.ac.jp.
³ Biochemistry Division, National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. nozaki@cc.osaka-dent.ac.jp.
⁴ Department of Pharmacology, Faculty of Dentistry, Osaka Dental University 8-1, Kuzuhahanazono-cho, Hirakata, Osaka 573-1121, Japan. nozaki@cc.osaka-dent.ac.jp.
⁵ Department of Pathology, Saiseikai Chuwa Hospital 323 Oaza Abe, Sakurai City, Nara 633-0054, Japan. mtutumi@chuwa-hp.jp.
⁶ Department of Frontier Life Sciences, Graduate School of Biochemical Science, Nagasaki University 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. bb55317036@ms.nagasaki-u.ac.jp.
⁷ Department of Oral Anatomy-1, School of Dental Medicine, Tsurumi University 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. shimoda-s@tsurumi-u.ac.jp.
⁸ Department of Oral and Maxillofacial Surgery, School of Dental Medicine, Tsurumi University 2-1-3 Tsurumi, Tsurumi-ku, Yokohama, Kanagawa 230-8501, Japan. hamada-y@tsurumi-u.ac.jp.
⁹ Biochemistry Division, National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. mmasutan@nagasaki-u.ac.jp.
¹⁰ Department of Frontier Life Sciences, Graduate School of Biochemical Science, Nagasaki University 1-7-1 Sakamoto, Nagasaki 852-8588, Japan. mmasutan@nagasaki-u.ac.jp.
¹¹ Division of Cellular Signaling, National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. mmasutan@nagasaki-u.ac.jp.

Abstract

Poly(ADP-ribose) polymerase (Parp)-1 catalyzes polyADP-ribosylation using NAD⁺ and is involved in the DNA damage response, genome stability, and transcription. In this study, we demonstrated that aged Parp-1^-/- mouse incisors showed more frequent dental dysplasia in both ICR/129Sv mixed background and C57BL/6 strain compared to aged Parp-1^+/+ incisors, suggesting that Parp-1 deficiency could be involved in development of dental dysplasia at an advanced age. Computed tomography images confirmed that dental dysplasia was observed at significantly higher incidences in Parp-1^-/- mice. The relative calcification levels of Parp-1^-/- incisors were higher in both enamel and dentin (p < 0.05). Immunohistochemical analysis revealed (1) Parp-1 positivity in ameloblasts and odontoblasts in Parp-1^+/+ incisor, (2) weaker dentin sialoprotein positivity in dentin of Parp-1^-/- incisor, and (3) bone sialoprotein positivity in dentin of Parp-1^-/- incisor, suggesting ectopic osteogenic formation in dentin of Parp-1^-/- incisor. These results indicate that Parp-1 deficiency promotes odontogenic failure in incisors at an advanced age. Parp-1 deficiency did not affect dentinogenesis during the development of mice, suggesting that Parp-1 is not essential in dentinogenesis during development but is possibly involved in the regulation of continuous dentinogenesis in the incisors at an advanced age.

Keywords: aged mice; dental dysplasia; knockout mice; poly(ADP-ribose) polymerase-1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Age Factors
Animals
Dental Pulp / metabolism
Dental Pulp / pathology*
Dentin Dysplasia / etiology*
Dentin Dysplasia / pathology
Female
Gene Expression Regulation, Developmental*
Incisor / metabolism
Incisor / pathology*
Male
Mice
Mice, Inbred C57BL
Mice, Inbred ICR
Mice, Knockout
Odontoblasts / metabolism
Odontoblasts / pathology*
Odontogenesis*
Poly (ADP-Ribose) Polymerase-1 / physiology*

Substances

Parp1 protein, mouse
Poly (ADP-Ribose) Polymerase-1