4.5 Article

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

Journal

CLINICAL ORAL INVESTIGATIONS
Volume 25, Issue 9, Pages 5307-5315

Publisher

SPRINGER HEIDELBERG
DOI: 10.1007/s00784-021-03839-2

Keywords

Root canal infection; Stem cells of the apical papilla; TNF-� � Regenerative endodontics; Endodontic pathogens; Macrophages

Funding

  1. Fonds Emile-Beaulieu
  2. AAE Foundation for Endodontics
  3. Canadian Academy of Endodontics Endowment Fund

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The study found that TNF- has detrimental effects on the viability, proliferation rate, and mineralization potential of stem cells of the apical papilla. Additionally, treating SCAP with TNF- reduced the secretion of periostin and increased the secretion of various cytokines and MMPs.
Objectives The first objective of the present study was to investigate TNF- secretion by macrophages stimulated with endodontic pathogens and bacterial cell surface components. The second objective was to assess the in vitro effects of TNF- 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- 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- were assessed using a colorimetric MTT assay. The mineralization potential of TNF--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- 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- by macrophages. The viability, proliferation rate, and mineralization activity of SCAP were negatively affected by a TNF- treatment. Treating SCAP with TNF- attenuated the secretion of periostin and upregulated the secretion of several cytokines and MMPs. Conclusions TNF- 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- can contribute to creating an inflammatory environment, promoting tissue destruction, and consequently interfering with the success of regenerative endodontic therapy.

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