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Orthodontic cell stress modifies proinflammatory cytokine expression in human PDL cells and induces immunomodulatory effects via TLR-4 signaling in vitro

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Abstract

Objective

Biomechanical orthodontics loading of the periodontium initiates a cascade of inflammatory signaling events that induce periodontal remodeling and finally facilitate orthodontic tooth movement. Pattern recognition receptors such as toll-like receptors (TLRs) have been well characterized for their ability to induce the activation of inflammatory, immunomodulatory cytokines. Here, we examined whether the cellular response of human periodontal ligament (hPDL) cells to mechanical stress involves TLR-4 signaling in vitro.

Materials and methods

Confluent hPDL cells were cultured in the presence of 5 μg/ml TLR-4 antibody (TLR-4ab) for 1 h prior to the induction of compressive forces by the use of round glass plates for 24 h. At harvest, interleukin-6 and interleukin-8 (IL-6, IL-8) mRNA and protein expression were analyzed by real-time PCR and ELISA. The immunomodulatory role of mechanical cell stress and TLR-4 signaling was addressed in co-culture experiments of hPDL and THP-1 cells targeting monocyte adhesion and by culturing osteoclastic precursors (RAW 264.7) in the presence of the conditioned medium of hPDL cells that had been mechanically loaded before.

Results

Basal expression of IL-6 and IL-8 was not affected by TLR-4ab, but increased significantly upon mechanical loading of hPDL cells. When cells were mechanically stressed in the presence of TLR-4ab, the effect seen for loading alone was markedly reduced. Likewise, monocyte adhesion and osteoclastic differentiation were enhanced significantly by mechanical stress of hPDL cells and this effect was partially inhibited by TLR-4ab.

Conclusions

The results of the present study indicate a proinflammatory and immunomodulatory influence of mechanical loading on hPDL cells. Intracellular signaling involves a TLR-4-dependent pathway.

Clinical relevance

These findings hold out the prospect of interfering with the cellular response to mechanical cell stress in order to minimize undesired side effects of orthodontic tooth movement.

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Acknowledgments

We thank the medical faculties of the University of Bonn and University of Aachen (both Germany) for their support of this research.

Funding

The work was supported by the University of Aachen, Department of Orthodontics, and University of Bonn, Department of Orthodontics.

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Author notes

  1. Jana Marciniak and Michael Wolf contributed equally to this work.

Authors and Affiliations

  1. Department of Orthodontics, Dental Clinic, University of Aachen, Pauwelsstr. 30, 52074, Aachen, Germany

    Jana Marciniak, Isabel Knaup, Asisa Bastian, Rogerio B. Craveiro & Michael Wolf

  2. Department of Orthodontics, Dental Clinic, University of Bonn, Bonn, Germany

    Jana Marciniak, Stefan Lossdörfer & Andreas Jäger

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  1. Jana Marciniak
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  2. Stefan Lossdörfer
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  6. Andreas Jäger
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Correspondence to Michael Wolf.

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This article does not contain any studies with human participants or animals performed by any of the authors. All experimental protocols were reviewed and approved by the ethics committee of the University of Bonn (reference number 029/08).

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Marciniak, J., Lossdörfer, S., Knaup, I. et al. Orthodontic cell stress modifies proinflammatory cytokine expression in human PDL cells and induces immunomodulatory effects via TLR-4 signaling in vitro. Clin Oral Invest 24, 1411–1419 (2020). https://doi.org/10.1007/s00784-019-03111-8

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  • DOI: https://doi.org/10.1007/s00784-019-03111-8

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