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首页> 外文期刊>Acta biomaterialia >The microRNA expression signature on modified titanium implant surfaces influences genetic mechanisms leading to osteogenic differentiation
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The microRNA expression signature on modified titanium implant surfaces influences genetic mechanisms leading to osteogenic differentiation

机译：修饰的钛植入物表面上的microRNA表达特征影响导致成骨分化的遗传机制

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Topographically and chemically modified titanium implants are recognized to have improved osteogenic properties; however, the molecular regulation of this process remains unknown. This study aimed to determine the microRNA profile and the potential regulation of osteogenic differentiation following early exposure of osteoprogenitor cells to sand-blasted, large-grit acid-etched (SLA) and hydrophilic SLA (modSLA) surfaces. Firstly, the osteogenic characteristics of the primary osteoprogenitor cells were confirmed using ALP activity and Alizarin Red S staining. The effect of smooth (SMO), SLA and modSLA surfaces on the TGF-β/BMP (BMP2, BMP6, ACVR1) and non-canonical WNT/Ca 2+ (WNT5A, FZD6) pathways, as well as the integrins ITGB1 and ITGA2, was determined. It was revealed that the modified titanium surfaces could induce the activation of TGF-β/BMP and non-canonical WNT/Ca 2+ signaling genes. The expression pattern of microRNAs (miRNAs) related to cell differentiation was evaluated. Statistical analysis of the differentially regulated miRNAs indicated that 35 and 32 miRNAs were down-regulated on the modSLA and SLA surfaces respectively, when compared with the smooth surface (SMO). Thirty-one miRNAs that were down-regulated were common to both modSLA and SLA. There were 10 miRNAs up-regulated on modSLA and nine on SLA surfaces, amongst which eight were the same as observed on modSLA. TargetScan predictions for the down-regulated miRNAs revealed genes of the TGF-β/BMP and non-canonical Ca 2+ pathways as targets. This study demonstrated that modified titanium implant surfaces induce differential regulation of miRNAs, which potentially regulate the TGF-β/BMP and WNT/Ca 2+ pathways during osteogenic differentiation on modified titanium implant surfaces.
机译：经地形和化学改性的钛植入物具有改善的成骨特性;然而，该过程的分子调控仍然未知。这项研究的目的是确定骨祖细胞早期暴露于喷砂，大粒度酸蚀（SLA）和亲水性SLA（modSLA）表面后的microRNA概况和成骨分化的潜在调控。首先，使用ALP活性和茜素红S染色证实了原代骨祖细胞的成骨特性。平滑（SMO），SLA和modSLA表面对TGF-β/ BMP（BMP2，BMP6，ACVR1）和非经典WNT / Ca 2+（WNT5A，FZD6）途径以及整合素ITGB1和ITGA2的影响，已确定。揭示了修饰的钛表面可以诱导TGF-β/ BMP和非经典的WNT / Ca 2+信号传导基因的激活。评价与细胞分化相关的微小RNA（miRNA）的表达模式。对差异调节的miRNA的统计分析表明，与光滑表面（SMO）相比，分别在modSLA和SLA表面上分别下调了35和32个miRNA。下调的31个miRNA是modSLA和SLA共有的。在modSLA上调了10个miRNA，在SLA表面上调了9个，其中有8个与在modSLA上观察到的相同。 TargetScan对下调的miRNA的预测揭示了TGF-β/ BMP和非规范Ca 2+途径的基因为靶标。这项研究表明修饰的钛植入物表面诱导了miRNA的差异调节，miRNA可能在修饰的钛植入物表面的成骨分化过程中调节TGF-β/ BMP和WNT / Ca 2+途径。

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