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Follicular dendritic cell-secreted protein gene expression is upregulated and spread in nifedipine-induced gingival overgrowth

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Abstract

Follicular dendritic cell-secreted protein (FDC-SP) is secreted protein expressed in follicular dendritic cells, periodontal ligament and junctional epithelium (JE). Its expression could be controlled during inflammatory process of gingiva; however, responsible mechanism for gingival overgrowth and involvement of FDC-SP in clinical condition is still unclear. We hypothesized that JE-specific genes are associated with the initiation of drug-induced gingival enlargement (DIGE) called gingival overgrowth, and investigated the changes of JE-specific gene’s expression and their localization in overgrown gingiva from the patients. Immunohistochemical analysis revealed that the FDC-SP localization was spread in overgrown gingival tissues. FDC-SP mRNA levels in GE1 and Ca9-22 cells were increased by time-dependent nifedipine treatments, similar to other JE-specific genes, such as Amelotin (Amtn) and Lamininβ3 subunit (Lamβ3), whereas type 4 collagen (Col4) mRNA levels were decreased. Immunocytochemical analysis showed that FDC-SP, AMTN, and Lamβ3 protein levels were increased in GE1 and Ca9-22 cells. Transient transfection analyses were performed using luciferase constructs including various lengths of human FDC-SP gene promoter, nifedipine increased luciferase activities of -345 and -948FDC-SP constructs. These results raise the possibility that the nifedipine-induced FDC-SP may be related to the mechanism responsible for gingival overgrowth does not occur at edentulous jaw ridges.

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Acknowledgements

The authors thank Dr. Shinomura T. Department of Hard Tissue Engineering, Tokyo Medical and Dental University, Tokyo, for sharing anti-FDC-SP antibodies.

Funding

This study was supported in part by the Japan Society for the Promotion of Science KAKENHI Grants, Grant-in-Aid for Scientific Research (C), Nos 17K11994 to YO, and 18K09582 to YN. Nihon University Multidisciplinary Research Grant (17-019) for 2017-2018 to YO, Discovery Grant RGPIN-2019-07070 from the Natural Sciences and Engineering Research Council (NSERC) and an Operating Grant MOP-119310 from the Canadian Institutes of Health Research (CIHR) to BG.

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Authors and Affiliations

  1. Department of Periodontology, Nihon University School of Dentistry At Matsudo, 2-870-1 Sakaecho-nishi, Matsudo, Chiba, 271-8587, Japan

    Yohei Nakayama, Eiko Inoue, Ayako Kato, Yasunobu Iwai, Mizuho Takai-Yamazaki, Yuto Tsuruya, Arisa Yamaguchi, Keisuke Noda & Yorimasa Ogata

  2. Research Institute of Oral Science, Nihon University School of Dentistry At Matsudo, Matsudo, Japan

    Yohei Nakayama, Ayako Kato, Takato Nomoto & Yorimasa Ogata

  3. Department of Special Needs Dentistry, Nihon University School of Dentistry At Matsudo, Matsudo, Japan

    Takato Nomoto

  4. Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, ON, Canada

    Bernhard Ganss

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  1. Yohei Nakayama
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Contributions

YN, BG and YO designed the study. YN, EI and TN collected samples. AK, YI, MTY, YT, AY and KN executed the experiments. YN performed the statistical analysis and finally analyzed the data and wrote the manuscript.

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Correspondence to Yohei Nakayama or Yorimasa Ogata.

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Nakayama, Y., Inoue, E., Kato, A. et al. Follicular dendritic cell-secreted protein gene expression is upregulated and spread in nifedipine-induced gingival overgrowth. Odontology 108, 532–544 (2020). https://doi.org/10.1007/s10266-020-00483-2

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