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Mitigative Effect of Erythromycin on PMMA Challenged Preosteoblastic MC3T3-E1 Cells

机译:红霉素对PMMA挑战的成骨前MC3T3-E1细胞的缓解作用

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摘要

Background. Aseptic loosening (AL) is a major complication of total joint replacement. Recent approaches to limiting AL have focused on inhibiting periprosthetic inflammation and osteoclastogenesis. Questions/Purposes. The purpose of this study was to determine the effects of erythromycin (EM) on polymethylmethacrylate (PMMA) particle-challenged MC3T3 osteoblast precursor cells. Methods. MC3T3 cells were pretreated with EM (0–10 μg/mL) and then stimulated with PMMA (1 mg/mL). Cell viability was evaluated by both a lactate dehydrogenase (LDH) release assay and cell counts. Cell differentiation was determined by activity of alkaline phosphatase (ALP). Gene expression was measured via real-time quantitative RT-PCR. Results. We found that exposure to PMMA particles reduced cellular viability and osteogenetic potential in MC3T3 cell line. EM treatment mitigated the effects of PMMA particles on the proliferation, viability and differentiation of MC3T3 cells. PMMA decreased the gene expression of Runx2, osterix and osteocalcin, which can be partially restored by EM treatment. Furthermore, EM suppressed PMMA- induced increase of NF-κB gene expression. Conclusions. These data demonstrate that EM mitigates the effects of PMMA on MC3T3 cell viability and differentiation, in part through downregulation of NF-κB pathway. EM appeared to represent an anabolic agent on MC3T3 cells challenged with PMMA particles.
机译:背景。无菌性松动(AL)是全关节置换的主要并发症。限制AL的最新方法集中于抑制假体周围炎症和破骨细胞生成。问题/目的。这项研究的目的是确定红霉素(EM)对聚甲基丙烯酸甲酯(PMMA)颗粒攻击的MC3T3成骨细胞前体细胞的影响。方法。 MC3T3细胞用EM(0-10μg/ mL)预处理,然后用PMMA(1μmg/ mL)刺激。通过乳酸脱氢酶(LDH)释放测定和细胞计数来评价细胞活力。细胞分化通过碱性磷酸酶(ALP)的活性来确定。通过实时定量RT-PCR测量基因表达。结果。我们发现暴露于PMMA颗粒会降低MC3T3细胞系的细胞活力和成骨潜能。 EM处理减轻了PMMA颗粒对MC3T3细胞增殖,活力和分化的影响。 PMMA降低了Runx2,osterix和骨钙蛋白的基因表达,这些基因表达可以通过EM治疗得到部分恢复。此外,EM抑制了PMMA诱导的NF-κB基因表达的增加。结论。这些数据表明,EM减轻了PMMA对MC3T3细胞活力和分化的影响,部分是通过下调NF-κB通路来实现的。 EM似乎代表了用PMMA颗粒攻击的MC3T3细胞的合成代谢药物。

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