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01.04.2015 | Original Article

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

verfasst von: Collin Jacobs, Christian Walter, Thomas Ziebart, Isabelle Dirks, Sabrina Schramm, Sarah Grimm, Elena Krieger, Heinrich Wehrbein

Erschienen in: Clinical Oral Investigations | Ausgabe 3/2015

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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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Titel: Mechanical loading influences the effects of bisphosphonates on human periodontal ligament fibroblasts
verfasst von: Collin Jacobs
Christian Walter
Thomas Ziebart
Isabelle Dirks
Sabrina Schramm
Sarah Grimm
Elena Krieger
Heinrich Wehrbein
Publikationsdatum: 01.04.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 3/2015
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-014-1284-4

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

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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Springer Medizin

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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