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09.09.2015 | Original Article

Altered macrophagic THP-1 cell phagocytosis and migration in bisphosphonate-related osteonecrosis of the jaw (BRONJ)

verfasst von: Sebastian Hoefert, Claudia Sade Hoefert, Adelheid Munz, Hinnak Northoff, Anna Yuan, Kathrin Reichenmiller, Siegmar Reinert, Martin Grimm

Erschienen in: Clinical Oral Investigations | Ausgabe 5/2016

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Abstract

Objectives

Local immune dysfunction via macrophages is a proposed aetiology of bisphosphonate-related osteonecrosis of the jaw (BRONJ). This study aimed to clarify the effects of various bisphosphonates on macrophage function using a THP-1 monocytic model to examine migration, phagocytosis, and fibrin structure.

Materials and methods

THP-1 cell migration was measured in the presence and absence of zoledronate, ibandronate, risedronate, alendronate, pamidronate (0.5, 5 and 50 μM) and clodronate (125, 250 and 500 μM) using the real-time xCELLigence system. Phagocytosis and actin fibre assays were performed after 72 h with zoledronate, ibandronate, alendronate and clodronate.

Results

Time to maximum migration for THP-1 cells was significantly reduced (p < 0.05) for high dosages of zoledronate, ibandronate and alendronate compared to controls. All dosages of clodronate and a low dose of zoledronate exhibited prolonged migrations. Phagocytic capacity was significantly reduced in high dosages of all bisphosphonates and for 5 μM zoledronate and ibandronate (p < 0.05). Low bisphosphonate exposure was accompanied by overcharged phagosoms. Altered appearance in F-actin fibrin structure was observed in bisphosphonate-exposed cells.

Conclusions

All bisphosphonates altered the migration of THP-1 cells dose-dependently. Low doses also prolonged migration and altered cell morphology. These findings support the idea of a disturbed local immune function of macrophages even in jaw bone exposed to low concentrations of bisphosphonate.

Clinical relevance

These are the first real-time results for disrupted migration and function of macrophagic THP-1 cells in high doses. Low dosages also demonstrated altered macrophage phagocytosis and cell morphology, suggesting a disturbed local immune function in BRONJ pathogenesis.

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Titel: Altered macrophagic THP-1 cell phagocytosis and migration in bisphosphonate-related osteonecrosis of the jaw (BRONJ)
verfasst von: Sebastian Hoefert
Claudia Sade Hoefert
Adelheid Munz
Hinnak Northoff
Anna Yuan
Kathrin Reichenmiller
Siegmar Reinert
Martin Grimm
Publikationsdatum: 09.09.2015
Verlag: Springer Berlin Heidelberg
Erschienen in: Clinical Oral Investigations / Ausgabe 5/2016
Print ISSN: 1432-6981
Elektronische ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-015-1584-3

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Abstract

Objectives

Materials and methods

Results

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Clinical relevance

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