MiR-490-3p inhibits osteogenic differentiation in thoracic ligamentum flavum cells by targeting FOXO1

被引:19
|
作者
Yang, Xiaoxi [1 ]
Qu, Xiaochen [2 ]
Meng, Xiangyu [3 ]
Li, Mengtao [3 ]
Fan, Dongwei [1 ]
Fan, Tianqi [1 ]
Huang, Ann Y. [4 ]
Chen, Zhongqiang [1 ]
Zhang, Chi [3 ,4 ,5 ]
机构
[1] Peking Univ, Hosp 3, Dept Orthoped, 49 North Garden Rd, Beijing 100191, Peoples R China
[2] Dalian Med Univ, Affiliated Hosp 1, Dept Orthoped, Dalian, Peoples R China
[3] Peking Univ, Int Hosp, Cent Lab, Beijing, Peoples R China
[4] Univ Texas Southwestern Med Ctr Dallas, Bone Res Lab, Dallas, TX 75390 USA
[5] Peking Univ, Dept Orthoped, Int Hosp, Beijing 102206, Peoples R China
来源
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2018年 / 14卷 / 11期
基金
中国国家自然科学基金;
关键词
thoracic ossification of the ligamentum flavum; miR-490-3p; osteogenic differentiation; FOXO1; BONE-FORMATION; OSTEOBLAST DIFFERENTIATION; STEM-CELLS; OSSIFICATION; EXPRESSION; MICRORNAS; REGULATOR; MODEL; OPLL;
D O I
10.7150/ijbs.26686
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thoracic ossification of the ligamentum flavum (TOLF) is a rare heterotopic ossification of spinal ligaments, which is the major cause of thoracic spinal canal stenosis and myelopathy. In this study, the roles of miR-490-3p and forkhead box O1 (FOXO1) in osteogenesis of human thoracic ligamentum flavum cells were investigated. MiR-490-3p was found to be down-regulated during osteogenic differentiation of thoracic ligamentum flavum cells, while their overexpression inhibited osteogenic differentiation. In addition, the analysis of target prediction and dual luciferase reporter assays supported that miR-490-3p directly targeted FOXO1 and suppressed the expression of FOXO1. Moreover, FOXO1 knockdown was displayed to attenuate the effect of miR-490-3p inhibition. ChIP assays showed that miR-490-3p negatively regulated the interaction of FOXO1 and RUNX2. These findings suggest that miR-490-3p performs an inhibitory role in osteogenic differentiation of thoracic ligamentum flavum cells by potentially targeting FOXO1.
引用
收藏
页码:1457 / 1465
页数:9
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