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Compressive force strengthened the pro-inflammatory effect of zoledronic acid on il-1ß stimulated human periodontal fibroblasts

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Abstract

Objectives

The number of patients in dentistry taking bisphosphonates (BP) increases every year. There are only little data about the influence of biomechanical stress due to orthodontic treatment and periodontal inflammation in BP patients. This study focused on the effects of the induced inflammation by IL-1ß in compressed human periodontal ligament fibroblasts (HPdLF) exposed to the nitrogen-containing BP zoledronate in vitro.

Materials and methods

HPdLF were incubated with 5 μmol/l zoledronate and 10 ng/ml IL-1ß for 48 h. In the last 3 h, cells were exposed to a compressive, centrifugal force of 34.9 g/cm2. Cell viability was analyzed directly after the compressive force by MTT assay. Gene expression of COX-2 and IL-6 was investigated using quantitative qRT-PCR. PGE-2 and IL-6 protein secretion were measured via ELISA.

Results

The cell viability of HPdLF was not affected. Without inflammatory pre-stimulation, COX-2 expression was increased by compression and zoledronate. IL-6 expression was increased under compression. On secretion level, the combination of compression and zoledronate induced a slightly increase of IL-6 secretion. In contrast, inflammatory pre-stimulation strengthened the compressive upregulation of COX-2, as well as induced a higher PGE-2 secretion. Further addition of zoledronate to pre-stimulated cells additionally strengthened the compression-induced upregulation of COX-2 and IL-6 expression as well as protein secretion compared to all other groups.

Conclusions

Biomechanical stress might trigger a pro-inflammatory potential of BP further enhanced in the presence of an inflammatory pre-stimulation.

Clinical relevance

To prevent excessive host inflammatory responses, occlusal overloading and mechanical stress due to orthodontic treatment should be avoided in BP patients with untreated periodontitis.

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Acknowledgments

Special thanks to Jutta Bühler and Dr. Jutta Goldschmitt for excellent technical assistance. Special thanks to Andrea Goetz for language help and proofreading.

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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, Ambili Mundethu & Heiner Wehrbein

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

    Judit Symmank, Christoph Hennig & Collin Jacobs

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

    Christian Walter

  4. Department of Pediatric Oral Health and Orthodontics, University of Basel, Mattenstraßsse 40, 4058, Basel, Switzerland

    Elisabeth Reichardt

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  1. Sarah Grimm
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Correspondence to Sarah Grimm.

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Author Sarah Grimm declares she has no conflict of interest. Author Ambili Mundethu declares she has no conflict of interest. Author Judit Symmank declares she has no conflict of interest. Author Christoph-Ludwig Hennig declares he has no conflict of interest. Author Christian Walter declares he has no conflict of interest. Author Elisabeth Reichardt declares she has no conflict of interest. Author Heiner Wehrbein declares he has no conflict of interest. Author Collin Jacobs declares he has no conflict of interest.

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Grimm, S., Mundethu, A., Symmank, J. et al. Compressive force strengthened the pro-inflammatory effect of zoledronic acid on il-1ß stimulated human periodontal fibroblasts. Clin Oral Invest 25, 3453–3461 (2021). https://doi.org/10.1007/s00784-020-03667-w

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