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首页> 外文期刊>Oral diseases >Alteration of macrophage viability, differentiation, and function by bisphosphonates
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Alteration of macrophage viability, differentiation, and function by bisphosphonates

机译：双膦酸盐改变巨噬细胞活力，分化和功能

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Abstract 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.
机译：摘要背景，长期双膦酸盐（BP）给药的严重不良影响是颌骨（Bronj）的双膦酸二族骨折。在不同的拟议发病机制中，免疫细胞的抑制是令人感兴趣的。因为单核细胞/巨噬细胞可以在血液和骨髓微环境中获得BP以获得BP，因此本研究的目的是分析体外BP治疗后巨噬细胞的行为。方法在本研究中使用THP -1细胞，一种已建立的人单核细胞模型。研究了BP S，Alendronate（ALN）和唑酸（ZA）对巨噬细胞活力，分化和功能的影响。进行MTT，形态学分析，流式细胞术，定量PCR和明胶酶测定法。结果BP S几乎所有浓度测试的巨噬细胞活力（1-100Ωμm）。在100μmbps的存在下，细胞形态被改变。此外，分化巨噬细胞活力也分别在100和10-100Ωμm处受AlN和Za的影响。在高浓度（100Ωμm），Za导致细胞分化的降低。相反，AlN和Za增加了基质金属蛋白酶mRNA表达和低剂量的活性（1-10Ωμm）。结论通过减少巨噬细胞存活，诱导形态改变，损害单核细胞对巨噬细胞的分化，并影响两种mRNA和活性水平的巨噬细胞功能，直接作用于巨噬细胞。

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