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Damage-regulated autophagy modulator 1 in oral inflammation and infection

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Abstract

Objectives

Damage-regulated autophagy modulator (DRAM) 1 is a p53 target gene with possible involvement in oral inflammation and infection. This study sought to examine the presence and regulation of DRAM1 in periodontal diseases.

Material and methods

In vitro, human periodontal ligament fibroblasts were exposed to interleukin (IL)-1β and Fusobacterium nucleatum for up to 2 days. The DRAM1 synthesis and its regulation were analyzed by real-time PCR, immunocytochemistry, and ELISA. Expressions of other autophagy-associated genes were also studied by real-time PCR. In vivo, synthesis of DRAM1 in gingival biopsies from rats and patients with and without periodontal disease was examined by real-time PCR and immunohistochemistry. For statistics, ANOVA and post-hoc tests were applied (p < 0.05).

Results

In vitro, DRAM1 was significantly upregulated by IL-1β and F. nucleatum over 2 days and a wide range of concentrations. Additionally, increased DRAM1 protein levels in response to both stimulants were observed. Autophagy-associated genes ATG3, BAK1, HDAC6, and IRGM were also upregulated under inflammatory or infectious conditions. In vivo, the DRAM1 gene expression was significantly enhanced in rat gingival biopsies with induced periodontitis as compared to control. Significantly increased DRAM1 levels were also detected in human gingival biopsies from sites of periodontitis as compared to healthy sites.

Conclusion

Our data provide novel evidence that DRAM1 is increased under inflammatory and infectious conditions in periodontal cells and tissues, suggesting a pivotal role of DRAM1 in oral inflammation and infection.

Clinical relevance

DRAM1 might be a promising target in future diagnostic and treatment strategies for periodontitis.

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Acknowledgements

The authors would like to thank Ms. Ramona Menden, Ms. Silke van Dyck, Ms. Inka Bay and Prof. Heiko Spallek for their valuable support.

Funding

This study was supported by the Medical Faculty of the University of Bonn, the University of Sydney, the German Orthodontic Society (DGKFO), the German Research Foundation (DFG, ME 4798/1–1) and by the German Federal Ministry of Education and Research (grant 01EK1603A-Neuro2D3, to AT).

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Authors and Affiliations

  1. Section of Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Welschnonnenstr. 17, 53111, Bonn, Germany

    Svenja Memmert, A. Damanaki, M. Nokhbehsaim & J. Deschner

  2. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany

    Svenja Memmert, B. Rath-Deschner, W. Götz & A. Jäger

  3. Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Sao Paulo State University, UNESP, Araraquara, Brazil

    A. V. B. Nogueira & J. A. Cirelli

  4. Department of Periodontology, Laboratory for Oral Microbiology, School of Dental Medicine, University of Bern, Bern, Switzerland

    S. Eick

  5. Department/Discipline of Periodontics, Faculty of Dentistry, The University of Sydney, Sydney, Australia

    T. Divnic-Resnik & A. Spahr

  6. Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn, Bonn, Germany

    A. Till

  7. Noel Martin Visiting Chair, Faculty of Dentistry, University of Sydney, Sydney, Australia

    J. Deschner

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  1. Svenja Memmert
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  2. A. V. B. Nogueira
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  3. A. Damanaki
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  9. A. Till
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  10. W. Götz
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Correspondence to Svenja Memmert.

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The authors declare that they have no conflict of interest.

Ethical approval

Approval of the Ethics Committee of the University of Bonn was obtained (#117/15 #043/11) and of the Ethical Committee on Animal Experimentation (protocol number: 23/2012) from the School of Dentistry at Araraquara. Animal experiments were carried out following the recommendations of the ARRIVE guidelines.

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All donors of the PDL cells or their parents gave written informed consent.

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Memmert, S., Nogueira, A.V.B., Damanaki, A. et al. Damage-regulated autophagy modulator 1 in oral inflammation and infection. Clin Oral Invest 22, 2933–2941 (2018). https://doi.org/10.1007/s00784-018-2381-6

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  • DOI: https://doi.org/10.1007/s00784-018-2381-6

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