Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138
Long non-coding RNA H19 mediates mechanical tension-induced osteogenesis of bone marrow mesenchymal stem cells via FAK by sponging miR-138
复制标题
长非编码 RNA H19 通过海绵 miR-138 通过 FAK 介导机械张力诱导的骨髓间充质干细胞成骨。
DOI：
10.1016/j.bone.2017.12.013
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发表时间：
2018-03-01
期刊：
影响因子：
4.1
通讯作者：
Zhang, Wei-Bing
中科院分区：
文献类型：
--
作者：
Wu, Jiajing;Zhao, Jing;Zhang, Wei-Bing
骨髓间充质干细胞（BMMSCs）为骨重建提供了生物学基础。机械张力刺激作为一种有效的调节剂能够促进BMMSCs的成骨能力。长链非编码RNA（LncRNA）作为与microRNA竞争的内源性RNA（ceRNA），被认为调节干细胞的成骨分化。然而，IncRNA如何（是否）介导BMSCs张力诱导成骨的机制仍然知之甚少。在此，使人BMMSC（hBMMSC）经受机械张力（10%，0.5Hz）。结果表明，机械张力可促进成骨分化，增加H19的表达。H19缺陷抑制张力诱导的成骨分化，表明H19可以介导hBMMSCs中张力诱导的成骨。此外，机械张力可抑制miR-138的表达，下调miR-138的表达可促进张力诱导的hBMMSCs成骨。荧光素酶报告基因分析表明H19与miR-138有结合位点，H19缺陷增加了miR-138的表达，表明H19可能作为miR-138的ceRNA在hBMMSCs中发挥作用。荧光素酶报告基因检测也显示miR-138可以靶向PTIQ，PTIQ是一种编码黏着斑激酶（FAR）的基因。上调的miR-138损害由机械张力诱导的FAR表达增加。进一步研究H19、miR-138和FAR在张力条件下的关系。H19缺陷抑制FAR表达，这可以通过敲低miR-138部分挽救。此外，H19缺陷细胞中抑制的张力诱导的成骨分化部分被miR-138敲低所挽救。综上所述，本研究表明H19通过充当miR-138的ceRNA，然后上调下游FAR，在张力诱导的hBMMSCs成骨中是正调节剂。(C)2018爱思唯尔公司All rights reserved.
Bone marrow mesenchymal stem cells (BMMSCs) provide the biological basis for bone reconstruction. Mechanical tension stimulation as a potent modulator is able to promote osteogenic capability of BMMSCs. Long non coding RNAs (LncRNAs) as competing endogenous RNAs (ceRNAs) for microRNAs, are postulated to regulate the osteogenic differentiation of stem cells. However, the mechanism how (whether) IncRNAs mediates tension-induced osteogenesis of BMSCs still remains poor understood. Here, human BMMSCs (hBMMSCs) were subjected to mechanical tension (10%, 0.5 Hz). Results showed that mechanical tension could enhance osteogenic differentiation and increase H19 expression. H19 deficiency suppressed tension-induced osteogenic differentiation, demonstrating that H19 could mediate tension-induced osteogenesis in hBMMSCs. Besides, mechanical tension could suppress miR-138 expression, and down-regulated miR-138 promoted tension induced osteogenesis in hBMMSCs. Luciferase reporter assays illustrated that H19 had binding sites with miR138, and H19 deficiency increased miR-138 level, demonstrating that H19 may act as a ceRNA for miR-138 in hBMMSCs. Luciferase reporter assays also showed that miR-138 could target PTIQ,a gene encoding focal adhesion kinase (FAR). Up-regulated miR-138 impaired increased FAR expression induced by mechaniCal tension. The relationship among H19, miR-138 and FAR under tension condition was further studied. H19 deficiency inhibited FAR expression, which could be partly rescued by knock-downing miR-138. In addition, suppressed tension-induced osteogenic differentiation in H19 defective cells was partly rescued by miR-138 knockdown. Taken together, this study indicated that H19 is a positive regulator in tension-induced osteogenesis of hBMMSCs through acting as a ceRNA for miR-138 and then up-regulating downstream FAR. (C) 2018 Elsevier Inc. All rights reserved.