Laxman Navya, Mallmin Hans, Nilsson Olle, Kindmark Andreas
Department of Medical Sciences, Uppsala University, Uppsala 75185, Sweden.
Science for Life Laboratory, Department of Medical Sciences, Uppsala University Hospital, Uppsala 75185, Sweden.
Genes (Basel). 2016 Dec 23;8(1):4. doi: 10.3390/genes8010004.
MicroRNAs (miRNAs) are a family of small, non-coding RNAs (17-24 nucleotides), which regulate gene expression either by the degradation of the target mRNAs or inhibiting the translation of genes. Recent studies have indicated that miRNA plays an important role in regulating osteoblast differentiation. In this study, we identified miR-203 and miR-320b as important miRNAs modulating osteoblast differentiation. We identified as potential common target by prediction algorithms and confirmed this by knock-down and over expression of the miRNAs and assessing at mRNA and protein levels and specificity was verified by luciferase reporter assays. We examined the effect of miR-203 and miR-320b on osteoblast differentiation by transfecting with pre- and anti-miRs. Over-expression of miR-203 and miR-320b inhibited osteoblast differentiation, whereas inhibition of miR-203 and miR-320b stimulated alkaline phosphatase activity and matrix mineralization. We show that miR-203 and miR-320b negatively regulate BMP-2-induced osteoblast differentiation by suppressing , which in turn suppresses the downstream osteogenic master transcription factor and and together they suppress osteoblast differentiation. Taken together, we propose a role for miR-203 and miR-320b in modulating bone metabolism.
微小RNA（miRNA）是一类小的非编码RNA（17 - 24个核苷酸），它们通过降解靶标mRNA或抑制基因翻译来调节基因表达。最近的研究表明，miRNA在调节成骨细胞分化中起重要作用。在本研究中，我们鉴定出miR - 203和miR - 320b是调节成骨细胞分化的重要miRNA。我们通过预测算法鉴定出[此处原文缺失具体内容]为潜在的共同靶标，并通过miRNA的敲低和过表达以及在mRNA和蛋白质水平评估[此处原文缺失具体内容]来证实这一点，荧光素酶报告基因检测验证了其特异性。我们通过转染前体miR和抗miR来检测miR - 203和miR - 320b对成骨细胞分化的影响。miR - 203和miR - 320b的过表达抑制成骨细胞分化，而抑制miR - 203和miR - 320b则刺激碱性磷酸酶活性和基质矿化。我们表明，miR - 203和miR - 320b通过抑制[此处原文缺失具体内容]来负向调节骨形态发生蛋白2（BMP - 2）诱导的成骨细胞分化，这反过来又抑制下游成骨主转录因子[此处原文缺失具体内容]和[此处原文缺失具体内容]，它们共同抑制成骨细胞分化。综上所述，我们提出miR - 203和miR - 320b在调节骨代谢中发挥作用。
