MicroRNA-141 and-200a Are Involved in Bone Morphogenetic Protein-2-induced Mouse Pre-osteoblast Differentiation by Targeting Distal-less Homeobox 5
MicroRNA-141 and-200a Are Involved in Bone Morphogenetic Protein-2-induced Mouse Pre-osteoblast Differentiation by Targeting Distal-less Homeobox 5
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DOI：
10.1074/jbc.m109.014001
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发表时间：
2009-07-17
影响因子：
4.8
通讯作者：
Akao, Yukihiro
中科院分区：
文献类型：
--
作者：
Itoh, Tomohiro;Nozawa, Yoshinori;Akao, Yukihiro
microRNA（miRs）是内源性表达的18-25个核苷酸的RNA，其通过与靶mRNA结合而通过翻译抑制来调节基因表达。最近，研究表明miR在细胞分化、细胞生长和细胞死亡中起关键调节剂的作用。在骨生成中，几种miR（例如miR-26 a、-125 b、-133和-135）调节人脂肪组织来源的干细胞、小鼠间充质ST 2干细胞和小鼠前肌源性C2 C12细胞中的成骨细胞生长或分化。此外，Smad蛋白控制Drosha介导的miR成熟。因此，miR与骨生成密切相关。在此，我们通过miR阵列研究了miR表达谱，并鉴定了候选miR-141和-200 a作为成骨细胞分化前相关的miR。通过使用成熟miR-141或-200a和miR-141或-200a的反义抑制剂转染小鼠前成骨细胞MC 3 T3-E1细胞来检查miR-141和-200a对前成骨细胞分化的影响。结果表明，miR-141和-200 a通过Dlx 5的翻译抑制显著调节BMP-2诱导的前成骨细胞分化，Dlx 5是在前成骨细胞分化中表达的骨生成转录因子。此外，通过使用荧光素酶报告基因测定，表明Dlx 5是miR-141和-200a的共同靶标。因此，我们首次观察到miR-141和-200a部分通过调节Dlx 5的表达参与前成骨细胞分化。
MicroRNAs (miRs) are endogenously expressed 18-25-nucleotide RNAs that regulate gene expression through translational repression by binding to a target mRNA. Recently, it was indicated that miRs act as key regulators in cell differentiation, cell growth, and cell death. In osteogenesis, several miRs ( for example miR-26a, -125b, -133, and -135) regulate osteoblast cell growth or differentiation in human adipose tissue-derived stem cells, mouse mesenchymal ST2 stem cells, and mouse premyogenic C2C12 cells. Additionally, Smad proteins control Drosha-mediated miR maturation. Therefore, miRs are closely related to osteogenesis. Here we investigated miR expression profile by an miR array and identified the candidate miRs, miR-141 and -200a, as pre-osteoblast differentiation-related miRs. The effects of miR-141 and -200a on pre-osteoblast differentiation were examined by using transfection of murine pre-osteoblastic MC3T3-E1 cells with mature miR-141 or -200a and antisense inhibitor for miR-141 or -200a. It was shown that miR-141 and -200a remarkably modulated the BMP-2-induced pre-osteoblast differentiation through the translational repression of Dlx5, which is a bone-generating transcription factor expressed in pre-osteoblast differentiation. Furthermore, it was indicated that Dlx5 is a common target of miR-141 and -200a by using a luciferase reporter assay. Thus, we have observed for the first time that miR-141 and -200a are involved in pre-osteoblast differentiation in part by regulating the expression of Dlx5.