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

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.

journal_name

Clin Oral Investig

authors

Hoefert S,Hoefert CS,Albert M,Munz A,Grimm M,Northoff H,Reinert S,Alexander D

doi

10.1007/s00784-014-1358-3

subject

Has Abstract

pub_date

2015-07-01 00:00:00

pages

1307-18

issue

6

eissn

1432-6981

issn

1436-3771

journal_volume

19

pub_type

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