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Mechanical loading influences the effects of bisphosphonates on human periodontal ligament fibroblasts

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Abstract

Objectives

There is increasing evidence that bisphosphonates affect orthodontic tooth movement. The object of the study was to investigate the changes produced by tensile strain on human periodontal ligament fibroblasts (HPdLFs) treated with clodronate or zoledronate.

Materials and methods

HPdLF were cultured with 5 and 50 μM clodronate or zoledronate for 48 h and applied to tensile strain (TS) (5 and 10 %) for 12 h in vitro. Viability was verified by MTT assay and apoptosis rate via caspase 3/7 assay. Gene expression of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG) was investigated using real-time PCR. OPG was also analyzed by ELISA and RANKL by immunocytochemical staining.

Results

Zoledronate (50 μM) reduced the viability of HPdLF (76 vs 100 %) and combined with 5 % TS to 53 %. TS of 10 % and clodronate reduced viability to 79 % with increased caspase 3/7 activity. Clodronate (5 μM) led to a slight increase of OPG gene expression, zoledronate (5 μM) to a slight decrease. Combined with 5 % TS, both increased OPG gene expression (2–3-fold) and OPG synthesis. Zoledronate increased gene expression of RANKL (4-fold). Combined with 5 % of TS, this increase was abolished. TS of 10 % in combination amplified increase of RANKL ending up with a 9-fold gene expression by clodronate and high RANKL protein synthesis.

Conclusions

This study shows for the first time that mechanical loading alters the effects of bisphosphonates on viability, apoptosis rate, and OPG/RANKL system of HPdLF dependent on the applied strength. Low forces and bisphosphonates increase factors for bone apposition, whereas high forces combined with bisphosphonates stimulate osteoclastogenesis.

Clinical relevance

Mechanical loading of periodontal ligament with high strengths should be avoided during bisphosphonate therapy.

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Acknowledgments

We thank Dr. Jutta Goldschmidt, Jutta Bühler, Ute Zerfass, and Lotte Groothusen for their assistance in the laboratory and Kathy Taylor for orthographic correction of the article.

Conflict of interest

The authors declare that no competing financial interest exists.

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Authors and Affiliations

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

    Collin Jacobs, Isabelle Dirks, Sabrina Schramm, Sarah Grimm, Elena Krieger & Heinrich Wehrbein

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

    Christian Walter & Thomas Ziebart

Authors
  1. Collin Jacobs
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  2. Christian Walter
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Correspondence to Collin Jacobs.

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Jacobs, C., Walter, C., Ziebart, T. et al. Mechanical loading influences the effects of bisphosphonates on human periodontal ligament fibroblasts. Clin Oral Invest 19, 699–708 (2015). https://doi.org/10.1007/s00784-014-1284-4

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  • DOI: https://doi.org/10.1007/s00784-014-1284-4

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