miR-3182调控LPPR4表达并抑制成骨细胞分化成熟的研究-中华老年骨科与康复电子杂志

文章信息/Info

Title:: MiR-3182 regulates LPPR4 expression and inhibits osteoblasts differentiation and maturation

作者:: 唐晓琳1; 孔霞2; 王槐高2; 李蓉2; 528300 佛山，顺德职业技术学院医药卫生学院1；523808 东莞广东医科大学病理生理学教研室2

Author(s):: Tang XiaoLin1; Kong Xia2; Wang Huaigao2; Li Rong2; 1Department of Medical Science, Shunde Polytechnic, Foshan 528300, China; 2Department of Physiopathology, Guangdong Medical University, Dongguan 523808, China

Keywords:: MicroRNA-3182; LPPR4 protein; Bone density; Gene Expression Omnibus (GEO) Database

摘要:: 目的本文通过细胞功能学实验探讨循环miR-3182和其靶基因磷酯磷酸化酶4（LPPR4）在成骨细胞分化成熟中的调控作用。方法本文通过对GEO数据GSE63446及GSE62402分析循环MicroRNA（miRNA）和组织表达谱信使RNA（mRNA）分别在人体低水平骨密度（BMD）与高水平BMD的表达谱的差异。对差异化表达的miRNA及其潜在调控靶点在表达谱芯片数据进行调控比对。对可能调控BMD水平的LPPR4基因进行过表达和微小RNA （siRNA）干扰方法研究其对人成骨细胞hFOB1.19分化成熟的研究。结果外周循环miR-3182在低BMD人群中显著高表达，其在区分高BMD和低BMD人群有非常好的敏感性和特异性。慢病毒质粒载体介导的miR-3182高表达显著降低细胞LPPR4基因mRNA水平和蛋白水平，并抑制成骨细胞hFOB1.19矿化结节形成。LPPR4蛋白高表达显著增加人成骨细胞hFOB1.19矿化结节的形成率和分化标志物OPG表达水平。结论受miR-3182调控的LPPR4基因促进成骨细胞分化。

Abstract:: Objective This study aims to reveal the regulatory effect of miR-3182 and its target LPPR4 on osteoblasts differentiation and maturation. Methods The study employed GSE63446 and GSE62402 datasets to reveal the association of circulating miRNA and tissue mRNA in bone mineral density (BMD). The two datasets were cross validated based on targets prediction. Plasmid mediated LPPR4 gene overexpression or siRNA interference was used to investigate its regulatory role in osteoblasts differentiation and maturation. Results Circulating miR-3182 was highly expressed in low BMD group, indicating excellent sensitivity and specificity in BMD classification. Lentivirus plasmind mediated miR-3182 expression decreased LPPR4 protein level and inhibited osteoblast hFOB1.19 mineralized nodules formation. Ectogenic overexpression of LPPR4 promoted hFOB1.19 cells mineralized nodule formation, and induced biomarker OPG expression. Conclusion LPPR4 promotes osteoblasts hFOB1.19 differentiation and maturation.