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Regulation of p53 under hypoxic and inflammatory conditions in periodontium

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Abstract

Objectives

Different studies suggest that inflammation as well as hypoxia leads to an increase of p53 protein levels. However, the implication of p53 during oral inflammatory processes is still unknown. The aim of this study was therefore to investigate the effect of hypoxia and inflammation on p53 regulation in human periodontium in vitro and in vivo.

Materials and methods

Under hypoxic and normoxic conditions, human primary periodontal ligament (PDL) fibroblasts (n = 9) were stimulated with lipopolysaccharides (LPS) from Porphyromonas gingivalis (P.g.), a periodontal pathogenic bacterium. After different time points, cell viability was tested; p53 gene expression, protein synthesis, and activation were measured using quantitative RT-PCR, immunoblotting, and immunofluorescence. Moreover, healthy and inflamed periodontal tissues were obtained from 12 donors to analyze p53 protein in oral inflammatory diseases by immunohistochemistry.

Results

LPS-P.g. and hypoxia initially induced a significant upregulation of p53 mRNA expression and p53 protein levels. Nuclear translocation of p53 after inflammatory stimulation supported these findings. Hypoxia first enhanced p53 levels, but after 24 h of incubation, protein levels decreased, which was accompanied by an improvement of PDL cell viability. Immunohistochemistry revealed an elevation of p53 immunoreactivity in accordance to the progression of periodontal inflammation.

Conclusions

Our data indicate that p53 plays a pivotal role in PDL cell homeostasis and seems to be upregulated in oral inflammatory diseases.

Clinical relevance

Upregulation of p53 may promote the destruction of periodontal integrity. A possible relationship with carcinogenesis may be discussed.

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Acknowledgments

The authors like to thank Tina Schaffrath, Inka Müller-Bay, and Elisa Vestewig for their technical support.

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Authors and Affiliations

  1. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Welschnonnenstr 17, 53111, Bonn, Germany

    S. Memmert, L. Gölz, P. Pütz, A. Jäger, B. Rath-Deschner & W. Götz

  2. Clinic and Polyclinic of Anesthesiology and Intensive Care Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany

    G. Baumgarten & S. Frede

  3. Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany

    S. Memmert & J. Deschner

  4. Clinic of Oral and Maxillofacial Surgery, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Bonn, Germany

    T. Appel

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  1. S. Memmert
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  2. L. Gölz
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Corresponding author

Correspondence to S. Memmert.

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Funding

The present study was supported by a grant from the German Research Foundation (Clinical Research Unit 208/TP7, TP9) and the Medical Faculty of the University of Bonn.

Conflict of interests

The authors declare that they have no competing interests.

Ethical approval

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. A vote of approval by the ethics committee of the Faculty of Medicine at the University of Bonn was obtained (Lfd.Nr 086/11).

Informed consent

Informed consent was obtained from all individual participants included in the study.

Additional information

S. Memmert, L. Gölz, S. Frede, and W. Götz contributed equally to this work.

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Memmert, S., Gölz, L., Pütz, P. et al. Regulation of p53 under hypoxic and inflammatory conditions in periodontium. Clin Oral Invest 20, 1781–1789 (2016). https://doi.org/10.1007/s00784-015-1679-x

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  • DOI: https://doi.org/10.1007/s00784-015-1679-x

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