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Production of TNF-𝛼 by macrophages stimulated with endodontic pathogens and its effect on the biological properties of stem cells of the apical papilla

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Abstract

Objectives

The first objective of the present study was to investigate TNF-𝛼 secretion by macrophages stimulated with endodontic pathogens and bacterial cell surface components. The second objective was to assess the in vitro effects of TNF-𝛼 on periostin, cytokine, and matrix metalloproteinase (MMP) secretion by and the viability, proliferation rate, and mineralization potential of stem cells of the apical papilla (SCAP).

Methods

TNF-𝛼 secretion by macrophages stimulated with either endodontic pathogens or bacterial surface components was assessed using an enzyme-linked immunosorbent assay (ELISA). The viability and proliferation rate of SCAP treated with TNF-𝛼 were assessed using a colorimetric MTT assay. The mineralization potential of TNF-𝛼-treated SCAP was determined by Alizarin Red staining. Periostin secretion by SCAP was determined by ELISA while cytokine and MMP secretion were assessed using a multiplexing laser bead assay.

Results

TNF-𝛼 secretion by macrophages increased following a stimulation with Gram-negative and Gram-positive endodontic pathogens. Lipopolysaccharide and lipoteichoic acid also dose-dependently increased the secretion of TNF-𝛼 by macrophages. The viability, proliferation rate, and mineralization activity of SCAP were negatively affected by a TNF-𝛼 treatment. Treating SCAP with TNF-𝛼 attenuated the secretion of periostin and upregulated the secretion of several cytokines and MMPs.

Conclusions

TNF-𝛼 exerts deleterious effects on SCAP by affecting their viability, proliferation rate, and mineralization potential. By its ability to induce the secretion of pro-inflammatory cytokines and MMPs by SCAP, TNF-𝛼 can contribute to creating an inflammatory environment, promoting tissue destruction, and consequently interfering with the success of regenerative endodontic therapy.

Clinical relevance

TNF-𝛼 has deleterious impacts on stem cells of the apical papilla and may compromise the outcome of regenerative endodontic therapy.

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Acknowledgements

We wish to thank K. Vaillancourt for her technical assistance.

Funding

The present study was supported by Fonds Émile-Beaulieu, the AAE Foundation for Endodontics, and the Canadian Academy of Endodontics Endowment Fund.

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Authors and Affiliations

  1. Oral Ecology Research Group, Faculty of Dentistry, Université Laval, 2420 rue de la Terrasse, Quebec City, QC, G1V 0A6, Canada

    Pierre-Olivier Miron, Amel Ben Lagha, Jabrane Azelmat, Juliana Nascimento Santos & Daniel Grenier

  2. Department of Endodontics, University of Texas Health Science Center at San Antonio, San Antonio, TX, USA

    Anibal Diogenes

Authors
  1. Pierre-Olivier Miron
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  2. Amel Ben Lagha
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  3. Jabrane Azelmat
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  4. Anibal Diogenes
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  5. Juliana Nascimento Santos
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  6. Daniel Grenier
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Contributions

Conceptualization: Daniel Grenier and Juliana Nascimento Santos. Formal analysis: Pierre-Olivier Miron, Amel Ben Lagha, and Jabrane Azelmat. Funding acquisition: Daniel Grenier and Juliana Nascimento Santos. Investigation and methodology: Pierre-Olivier Miron, Amel Ben Lagha, Jabrane Azelmat, Juliana Nascimento Santos, Anibal Diogenes, and Daniel Grenier. Project administration: Daniel Grenier. Supervision: Daniel Grenier. Writing—original draft: Pierre-Olivier Miron. Writing—review and editing: Juliana Nascimento Santos, Anibal Diogenes, and Daniel Grenier.

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Correspondence to Daniel Grenier.

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The present study did not involve any experiments with human participants.

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The authors declare no competing interests.

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Miron, PO., Ben Lagha, A., Azelmat, J. et al. Production of TNF-𝛼 by macrophages stimulated with endodontic pathogens and its effect on the biological properties of stem cells of the apical papilla. Clin Oral Invest 25, 5307–5315 (2021). https://doi.org/10.1007/s00784-021-03839-2

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  • DOI: https://doi.org/10.1007/s00784-021-03839-2

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