MiR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion.
MiR-9-5p, miR-675-5p and miR-138-5p Damages the Strontium and LRP5-Mediated Skeletal Cell Proliferation, Differentiation, and Adhesion.
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DOI：
10.3390/ijms17020236
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发表时间：
2016-02-15
影响因子：
5.6
通讯作者：
Lu WW
中科院分区：
文献类型：
--
作者：
Sun T;Leung F;Lu WW
本研究旨在评估锶对microRNA（miRNAs）表达水平的影响，并探讨其对骨骼肌细胞增殖、分化、粘附和凋亡的影响。我们还研究了这些miRNAs的靶点。采用分子克隆、细胞增殖试验、细胞凋亡试验、实时荧光定量PCR和荧光素酶报告基因试验。锶改变了miRNAs在体外和体内的表达水平。miR-9- 5 p、miR-675- 5 p和miR-138- 5 p损害骨骼细胞增殖、细胞分化和细胞粘附。miR-9- 5 p和miR-675- 5 p诱导MC 3 T3-E1细胞凋亡的特异性高于miR-138- 5 p。miR-9- 5 p、miR-675- 5 p和miR-138- 5 p分别靶向糖原合成酶激酶3 β（GSK 3 β）、ATP酶氨基磷脂转运蛋白I类8A型成员2（ATP 8A 2）和真核翻译起始因子4 E结合蛋白1（EIF 4 EBP 1）。低密度脂蛋白受体相关蛋白5（LRP 5）在骨骼发育中起积极作用。miR-9- 5 p、miR-675- 5 p和miR-138- 5 p分别通过靶向GSK 3 β、ATP 8A 2和EIF 4 EBP 1损伤锶和LRP 5介导的骨骼细胞增殖、分化和粘附，并诱导细胞凋亡。
This study was designed to evaluate the effects of strontium on the expression levels of microRNAs (miRNAs) and to explore their effects on skeletal cell proliferation, differentiation, adhesion, and apoptosis. The targets of these miRNAs were also studied. Molecular cloning, cell proliferation assay, cell apoptosis assay, quantitative real-time PCR, and luciferase reporter assay were used. Strontium altered the expression levels of miRNAs in vitro and in vivo. miR-9-5p, miR-675-5p, and miR-138-5p impaired skeletal cell proliferation, cell differentiation and cell adhesion. miR-9-5p and miR-675-5p induced MC3T3-E1 cell apoptosis more specifically than miR-138-5p. miR-9-5p, miR-675-5p, and miR-138-5p targeted glycogen synthase kinase 3 β (GSK3β), ATPase Aminophospholipid Transporter Class I Type 8A Member 2 (ATP8A2), and Eukaryotic Translation Initiation Factor 4E Binding Protein 1 (EIF4EBP1), respectively. Low-density lipoprotein receptor-related protein 5 (LRP5) played a positive role in skeletal development. miR-9-5p, miR-675-5p, and miR-138-5p damage strontium and LRP5-mediated skeletal cell proliferation, differentiation, and adhesion, and induce cell apoptosis by targeting GSK3β, ATP8A2, and EIF4EBP1, respectively.