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阿伦膦酸盐和唑来膦酸盐对人成骨细胞、牙龈成纤维细胞和骨肉瘤细胞的细胞毒性和炎症作用。

Cytotoxic and inflammatory effects of alendronate and zolendronate on human osteoblasts, gingival fibroblasts and osteosarcoma cells.

机构信息

Christian Albrechts University, Department of Oral and Maxillofacial Surgery, Kiel, Germany.

Private Practice, Duisburg, Germany.

出版信息

J Craniomaxillofac Surg. 2018 Apr;46(4):538-546. doi: 10.1016/j.jcms.2017.12.015. Epub 2018 Jan 10.

Abstract

OBJECTIVE

The aim of this paper was to assess the effects of zoledronate (ZOL) and alendronate (FOS) on apoptotic behavior and gene expression of pro- and inflammatory cytokines of three cell types (human osteoblasts, human gingival fibroblasts and human osteogenic sarcoma cell lines) during a period of 4 weeks.

MATERIAL AND METHODS

Cell viability and proliferation was assessed via cell proliferation test (MTT), fluorescence diacetate analysis (FDA). Expression of inflammatory cytokines was investigated by using polymerase chain reaction.

RESULTS

The proliferation and cell vitality of osteoblasts and fibroblasts were negatively affected in a dose dependent manner under ZOL and FOS administration. Osteosarcoma cells showed an increase in proliferation under lower doses of BP. ZOL had a significantly higher cytotoxic effect compared with FOS on osteoblasts and fibroblasts. ZOL increased the production of IL-6 in all cell types, whereas FOS only in osteosarcoma cell, which happened in dose dependent manner. Bisphosphonates could result in increase of IL-1β expression of fibroblasts. An increase of IL-12 was observed at higher doses of ZOL administration among osteoblasts and FOS administration in osteosarcoma cells.

CONCLUSION

ZOL and FOS could encourage cytotoxic and inflammatory reactions.

摘要

目的

本文旨在评估唑来膦酸(zoledronate,ZOL)和阿仑膦酸钠(alendronate,FOS)对三种细胞类型(人成骨细胞、人牙龈成纤维细胞和人骨肉瘤细胞系)在 4 周内的凋亡行为和促炎细胞因子基因表达的影响。

材料与方法

通过细胞增殖试验(MTT)和荧光二乙酸分析(FDA)评估细胞活力和增殖。采用聚合酶链反应(PCR)检测炎症细胞因子的表达。

结果

在 ZOL 和 FOS 给药下,成骨细胞和成纤维细胞的增殖和细胞活力呈剂量依赖性降低。骨肉瘤细胞在较低剂量 BP 下增殖增加。ZOL 对成骨细胞和成纤维细胞的细胞毒性作用明显高于 FOS。ZOL 增加了所有细胞类型中 IL-6 的产生,而 FOS 仅在骨肉瘤细胞中增加,且呈剂量依赖性。双膦酸盐可导致成纤维细胞 IL-1β 表达增加。在较高剂量的 ZOL 给药时观察到成骨细胞中 IL-12 增加,在骨肉瘤细胞中 FOS 给药时增加。

结论

ZOL 和 FOS 可促进细胞毒性和炎症反应。

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