miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration.
miR-142-5p in Bone Marrow-Derived Mesenchymal Stem Cells Promotes Osteoporosis Involving Targeting Adhesion Molecule VCAM-1 and Inhibiting Cell Migration.
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骨髓间充质干细胞中的 miR-142-5p 促进骨质疏松症，涉及靶向粘附分子 VCAM-1 和抑制细胞迁移
DOI：
10.1155/2018/3274641
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发表时间：
2018
影响因子：
--
通讯作者：
Xian CJ
中科院分区：
文献类型：
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作者：
Teng Z;Xie X;Zhu Y;Liu J;Hu X;Na Q;Zhang X;Wei G;Xu S;Liu Y;Zhang X;Xian CJ
骨质疏松症是一种全身性骨代谢疾病，在老年人群中非常普遍，特别是在绝经后妇女中，其导致骨脆性增强和骨折易感性增加。然而，其致病的分子机制仍有待进一步阐明。在本研究中，通过RNA测序分析和qRT-PCR，在大鼠卵巢切除术（OVX-）诱导的绝经后骨质疏松症模型中，发现microRNA miR-142- 5 p和血管细胞粘附分子1（VCAM-1）的异常表达。使用双荧光素酶报告基因分析，我们发现miR-142- 5 p可以结合并降低VCAM-1 mRNA的表达。当VCAM-1 3′UTR中的miR-142- 5 p结合位点被删除时，这种减少被抑制，并且Western blotting分析证实了miR-142- 5 p抑制VCAM-1蛋白表达的事实。转染miR-142- 5 p的骨髓间充质干细胞（BMMSCs）在Transwell迁移试验中显示出显著降低的迁移能力。总之，这些数据表明miR-142- 5 p在骨质疏松症发展中的重要作用，涉及靶向VCAM-1和抑制BMMSC迁移。
Osteoporosis is a systemic bone metabolic disease that is highly prevalent in the elderly population, particularly in postmenopausal women, which results in enhanced bone fragility and an increased susceptibility to fractures. However, the underlying molecular pathogenesis mechanisms still remain to be further elucidated. In this study, in a rat ovariectomy- (OVX-) induced postmenopausal osteoporosis model, aberrant expression of a microRNA miR-142-5p and vascular cell adhesion molecule 1 (VCAM-1) was found by RNA sequencing analysis and qRT-PCR. Using a dual-luciferase reporter assay, we found that miR-142-5p can bind to and decrease expression of VCAM-1 mRNA. Such reduction was prohibited when the miR-142-5p binding site in VCAM-1 3′UTR was deleted, and Western blotting analyses validated the fact that miR-142-5p inhibited the expression of VCAM-1 protein. Bone marrow-derived mesenchymal stem cells (BMMSCs) transfected with miR-142-5p showed a significantly decreased migration ability in a Transwell migration assay. Collectively, these data indicated the important role of miR-142-5p in osteoporosis development involving targeting VCAM-1 and inhibiting BMMSC migration.