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

机译:辛伐他汀诱导人原发性骨盆的增殖和矿化的不利影响

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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. 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. 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. 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.
机译:施用经常毒素以降低循环血液中的LDL浓度。特别是辛伐他汀(SV)是通常规定的他汀类药物。报道了这些药物的脂肪效应。因此,本研究的目的是评估SV对骨细胞髓质化的影响。经过知情的同意,在治疗Cranio-Maxilloacial手术部,大学医院Münster的14人后,从组织剩余中收集原发性骨细胞。根据已建立的方案传代细胞。在加入各种SV浓度(0.05Ωμm,0.1Ωμm,0.5Ωμm,1.0≤μm)后,在第9,13和16天测定活力,矿化能力和成骨细胞标记物(碱性磷酸酶)。使用Kruskal-Wallis-Test进行统计分析。细胞培养物显示时间和剂量依赖性显着降低的活力(P?<β01),在添加SV后,在晚期矿化阶段中显着增加的矿化(p?<0.01)。骨质发生分化期间碱性磷酸酶(ALP)水平的典型改变无法识别。发现不同SV浓度的脂肪效应可能来自ALP诱导旁边的其他矿化途径。另外,在受影响机制的更深层次的洞察力之后,可以考虑矿化过程中蛋白质表达水平的蛋白质表达水平的可能改变,并且可以在受影响机制的更深层次的洞察力之后考虑。

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