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Alteration of macrophage viability, differentiation, and function by bisphosphonates
Author(s) -
Patntirapong Somying,
Poolgesorn Mahatana
Publication year - 2018
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.12908
Subject(s) - macrophage , viability assay , flow cytometry , zymography , osteonecrosis of the jaw , mtt assay , m2 macrophage , matrix metalloproteinase , immune system , chemistry , bisphosphonate , cell growth , cancer research , cell , immunology , in vitro , medicine , biochemistry , osteoporosis
Background A serious adverse effect of long‐term bisphosphonate ( BP ) administration is bisphosphonate‐related osteonecrosis of the jaw ( BRONJ ). Among different proposed pathogenesis, suppression of immune cells is gaining interest. Because monocytes/macrophages could get access to BP since residing in the blood and bone microenvironment, the aim of this study was to analyze the behaviors of macrophages after BP treatments in vitro. Methods THP ‐1 cell, an established human monocytic cell model, was used in this study. The effects of BP s, alendronate ( ALN ) and zoledronic acid ( ZA ), on macrophage viability, differentiation, and function were investigated. MTT , morphological analysis, flow cytometry, quantitative PCR , and gelatin zymography assay were performed. Results BP s impaired macrophage viability at almost all concentration tested (1–100 μM). Cell morphology was altered in the presence of 100 μM BP s. Furthermore, differentiating macrophage viability was also affected by both ALN and ZA at 100 and 10–100 μM, respectively. At high concentration (100 μM), ZA caused a reduction in cell differentiation. On the contrary, ALN and ZA increased matrix metalloproteinase mRNA expressions and activities at low doses (1–10 μM). Conclusion BP s directly acted on macrophage by reducing macrophage survival, inducing morphological alterations, impairing differentiation from monocytes to macrophages, and affecting macrophage function at both mRNA and activity levels.