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Influence of clodronate and compressive force on IL-1ß-stimulated human periodontal ligament fibroblasts

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Abstract

Objectives

The aim of this study was to investigate in vitro the effect of clodronate on interleukin-1ß (IL-1ß)–stimulated human periodontal ligament fibroblasts (HPdLFs) with the focus on inflammatory factors of orthodontic tooth movement with and without compressive force.

Materials and methods

HPdLFs were incubated with 5 μM clodronate and 10 ng/mL IL-1ß. After 48 h, cells were exposed to 3 h of compressive force using a centrifuge. The gene expression of cyclooxygenase-2 (COX-2), interleukin-6 (IL-6), matrix metalloproteinase 8 (MMP-8), and the tissue inhibitor of MMP (TIMP-1) was analyzed using RT-PCR. Prostaglandin E2 (PGE-2), IL-6, and TIMP-1 protein syntheses were quantified via ELISA.

Results

Compressive force and IL-1ß induced an overexpression of COX-2 gene expression (61.8-fold; p < 0.05 compared with control), diminished by clodronate (41.1-fold; p < 0.05 compared with control). Clodronate slowed down the compression and IL-1ß induced IL-6 gene expression (161-fold vs. 85.6-fold; p < 0.05 compared with control). TNF-α was only slightly affected without statistical significance. Clodronate reduced IL-1ß-stimulated MMP-8 expression with and without compressive force. TIMP-1 on gene and protein level was downregulated in all groups. Analyzing the MMP-8/TIMP-1 ratio, the highest ratio was detected in IL-1ß-stimulated HPdLFs with compressive force (21.2-fold; p < 0.05 compared with control). Clodronate diminished IL-1ß-induced upregulation of MMP-8/TIMP-1 ratio with (11.5-fold; p < 0.05 compared with control) and without (12.5-fold; p < 0.05 compared with control) compressive force.

Conclusion

Our study demonstrates a slightly anti-inflammatory effect by clodronate under compressive force in vitro. Additionally, the periodontal remodeling presented by the MMP-8/TIMP-1 ratio seems to be diminished by clodronate.

Clinical relevance

Reduction of pro-inflammatory factors and reduction of periodontal remodeling might explain reduced orthodontic tooth movement under clodronate intake.

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Funding

The work was supported by the Osteology Foundation (Lucerne, Switzerland).

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Authors and Affiliations

  1. Department of Orthodontics, University Medical Centre, Johannes Gutenberg University Mainz, Augustusplatz 2, 55131, Mainz, Germany

    Sarah Grimm, Eva Wolff, Ambili Mundethu & Heiner Wehrbein

  2. Department of Oral and Maxillofacial Surgery, University Medical Centre, Johannes Gutenberg University Mainz, Augustusplatz 2, 55131, Mainz, Germany

    Christian Walter & Andreas M. Pabst

  3. Department of Traumatology, University of Bonn, Sigmund-Freud-Straße 25, 53127, Bonn, Germany

    Cornelius Jacobs

  4. Department of Orthodontics, University of Jena, An der Alten Post 4, 07743, Jena, Germany

    Collin Jacobs

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  1. Sarah Grimm
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Correspondence to Sarah Grimm.

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Grimm, S., Wolff, E., Walter, C. et al. Influence of clodronate and compressive force on IL-1ß-stimulated human periodontal ligament fibroblasts. Clin Oral Invest 24, 343–350 (2020). https://doi.org/10.1007/s00784-019-02930-z

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