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Clinical Oral Investigations
Published in: Clinical Oral Investigations 6/2015

01-07-2015 | Original Article

Zoledronate but not denosumab suppresses macrophagic differentiation of THP-1 cells. An aetiologic model of bisphosphonate-related osteonecrosis of the jaw (BRONJ)

Authors: Sebastian Hoefert, Claudia Sade Hoefert, Marc Albert, Adelheid Munz, Martin Grimm, Hinnak Northoff, Siegmar Reinert, Dorothea Alexander

Published in: Clinical Oral Investigations | Issue 6/2015

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Abstract

Objectives

Bisphosphonates and denosumab are antiresorptive drugs used for the treatment of osteoporosis and oncological tumors. A severe side effect is osteonecrosis of the jaw. Monocyte/macrophage dysfunction is considered to play a distinct role in osteonecrosis. THP-1 monocytic cells were used in this study to elucidate the influence of zoledronate and denosumab on phorbol-12-myrisate-13-acetate (PMA)-induced macrophage differentiation and function in real-time.

Materials and methods

Macrophagic differentiation of the THP-1 suspension cells was measured by cell adherence in the presence or absence of different concentrations of zoledronate (0.5, 5, 50 μM) and denosumab (1, 10, 20, 40 μg/mL) using the real-time xCELLigence system. Additionally, a live/dead staining was performed by fluorescence microscopy.

Results

THP-1 cells demonstrated a regular initial PMA-induced differentiation to macrophages by live measurements of cell adherence and by an increase in CD68 surface expression as detected by flow cytometry. The addition of zoledronate led to cell detachment of the THP-1-derived macrophages in a dose-dependent manner in contrast to denosumab. Cell detachment was based on cell death as confirmed by live/dead staining, revealing elevated numbers of dead cells following addition of high zoledronate concentrations. However, denosumab did not deteriorate THP-1 cell viability.

Conclusion

Our results demonstrate that zoledronate but not denosumab suppresses monocytic THP-1 cell viability after macrophagic differentiation dose-dependently.

Clinical relevance

This is the first real-time study providing evidence for a dose-dependent immunosuppressive effect of zoledronate in contrast to denosumab on local macrophages.
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Metadata
Title
Zoledronate but not denosumab suppresses macrophagic differentiation of THP-1 cells. An aetiologic model of bisphosphonate-related osteonecrosis of the jaw (BRONJ)
Authors
Sebastian Hoefert
Claudia Sade Hoefert
Marc Albert
Adelheid Munz
Martin Grimm
Hinnak Northoff
Siegmar Reinert
Dorothea Alexander
Publication date
01-07-2015
Publisher
Springer Berlin Heidelberg
Published in
Clinical Oral Investigations / Issue 6/2015
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI
https://doi.org/10.1007/s00784-014-1358-3

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