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辛伐他汀对人原代成骨细胞的增殖和矿化有不良影响。

Simvastatin induces adverse effects on proliferation and mineralization of human primary osteoblasts.

作者信息

Sabandal Martin Mariano Isabelo, Schäfer Edgar, Aed Jonathan, Jung Susanne, Kleinheinz Johannes, Sielker Sonja

机构信息

Central Interdisciplinary Ambulance in the School of Dentistry, University of Münster, Albert-Schweitzer-Campus 1, Gebäude W30, Waldeyerstr. 30, 48149, Münster, Germany.

Department of Cranio-Maxillofacial Surgery, University Hospital Münster, Münster, Germany.

出版信息

Head Face Med. 2020 Aug 20;16(1):18. doi: 10.1186/s13005-020-00232-4.

Abstract

BACKGROUND

Frequently statins were administered to reduce the LDL-concentration in circulating blood. Especially simvastatin (SV) is an often prescribed statin. Pleiotropic effects of these drugs were reported. Thus, the aim of this study was to evaluate effects of SV on osteoblastic mineralization.

METHODS

After informed consent primary osteoblasts were collected from tissue surplus after treatment of 14 individuals in the Department of Cranio-Maxillofacial Surgery, University Hospital Münster. The cells were passaged according to established protocols. Viability, mineralization capability and osteoblastic marker (alkaline phosphatase) were determined at day 9, 13 and 16 after adding various SV concentrations (0.05 μM, 0.1 μM, 0.5 μM, 1.0 μM). Statistical analysis was performed using the Kruskal-Wallis-test.

RESULTS

The cell cultures showed a time and dose-dependent significantly decreased viability (p < 0.01) and a significantly increased mineralization (p < 0.01) in a late mineralization stage after adding SV. The typical alteration of the alkaline phosphatase (ALP) levels during osteogenic differentiation was not recognizable.

CONCLUSIONS

The pleiotropic effects found for different SV concentrations were possibly originated from other mineralization pathways beside the ALP induced one. Additionally, possible alterations of protein expression levels during mineralization and investigation of possible deviating application of SV in other treatment fields can be considered after gaining a deeper insight in the affected mechanisms.

摘要

背景

他汀类药物常用于降低循环血液中的低密度脂蛋白浓度。特别是辛伐他汀(SV)是一种常用的他汀类药物。这些药物具有多效性。因此,本研究的目的是评估SV对成骨细胞矿化的影响。

方法

在获得知情同意后,从明斯特大学医院颅颌面外科治疗的14名患者的多余组织中收集原代成骨细胞。细胞按照既定方案传代。在添加不同浓度的SV(0.05μM、0.1μM、0.5μM、1.0μM)后第9、13和16天测定细胞活力、矿化能力和成骨细胞标志物(碱性磷酸酶)。采用Kruskal-Wallis检验进行统计分析。

结果

添加SV后,细胞培养物在矿化后期显示出时间和剂量依赖性的显著活力下降(p<0.01)和显著矿化增加(p<0.)。在成骨分化过程中碱性磷酸酶(ALP)水平的典型变化无法识别。

结论

不同浓度SV的多效性作用可能源于除ALP诱导途径之外的其他矿化途径。此外,在更深入了解受影响机制后,可以考虑矿化过程中蛋白质表达水平的可能变化以及SV在其他治疗领域可能的不同应用研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4587/7439668/cec6cb2340bd/13005_2020_232_Fig1_HTML.jpg

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