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首页> 外文期刊>Journal of cellular biochemistry. >Parathyroid hormone‐induced down‐regulation of miR‐532‐5p for matrix metalloproteinase‐13 expression in rat osteoblasts
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Parathyroid hormone‐induced down‐regulation of miR‐532‐5p for matrix metalloproteinase‐13 expression in rat osteoblasts

机译:甲状旁腺激素诱导大鼠成骨细胞中基质金属蛋白酶-13表达的miR-532-5p的下调

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Abstract Parathyroid hormone (PTH) acts on osteoblasts and functions as an essential regulator of calcium homeostasis and as a mediator of bone remodeling. We previously reported that PTH stimulates the expression of matrix metalloproteinase‐13 (MMP‐13) in rat osteoblasts and that MMP‐13 plays a key role in bone remodeling, endochondral bone formation, and bone repair. Recent evidence indicated that microRNAs (miRNAs) have regulatory functions in bone metabolism. In this study, we hypothesized that the down‐regulation of miRNAs that target MMP‐13 by PTH leads to the stimulation of MMP‐13 expression in osteoblasts. We used various bioinformatic tools to identify miRNAs that putatively target rat MMP‐13. Among these miRNAs, the expression of miR‐532‐5p in rat osteoblasts decreased at 4?h of PTH‐treatment, whereas MMP‐13 mRNA expression was maximal at the same time point. When an miR‐532‐5p mimic was transiently transfected into UMR‐106‐01 cells, MMP‐13 mRNA and protein expression decreased. Using a luciferase reporter assay system, we also identified that miR‐532‐5p directly targeted the 3′ UTRs of MMP‐13 gene. Based on these results, we suggest that PTH‐induced down‐regulation of miR‐532‐5p resulted in the stimulation of MMP‐13 expression in rat osteoblasts. This study identified a significant role of miRNA in controlling bone remodeling via PTH‐stimulated MMP‐13 expression. This finding enhances our understanding of bone metabolism and bone‐related diseases and it could provide information regarding the usage of miRNAs as therapeutic agents or biomarkers.
机译:摘要甲状旁腺激素(PTH)作用于成骨细胞,用作钙稳态的必需调节剂,作为骨重塑的介质。我们以前报道,PTH刺激大鼠成骨细胞中基质金属蛋白酶-13(MMP-13)的表达,并且MMP-13在骨重塑,中间骨形成和骨骼修复中起关键作用。最近的证据表明MicroRNA(miRNA)具有骨代谢的调节功能。在这项研究中,我们假设通过PTH靶向MMP-13的miRNA的下调导致在成骨细胞中的MMP-13表达的刺激。我们使用各种生物信息工具来识别尺寸靶标大鼠MMP-13的miRNA。在这些miRNA中,大鼠成骨细胞中miR-532-5p的表达在Pth治疗的4℃下降,而MMP-13mRNA表达在同一时间点最大。当miR-532-5p模拟物瞬时转染到UMR-106-01细胞中时,MMP-13 mRNA和蛋白质表达减少。使用荧光素酶报告系统测定系统,我们还鉴定了MIR-532-5P直接靶向MMP-13基因的3'UTR。基于这些结果,我们建议PTH诱导的miR-532-5p的下调导致大鼠成骨细胞中的MMP-13表达刺激。该研究确定了miRNA在通过PTH刺激的MMP-13表达控制骨重塑方面的重要作用。这一发现提高了我们对骨代谢和骨骼相关疾病的理解,它可以提供有关MiRNA作为治疗剂或生物标志物的信息。

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