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Int J Biol Sci 2018; 14(11):1457-1465. doi:10.7150/ijbs.26686

Research Paper

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

Xiaoxi Yang1, Xiaochen Qu2, Xiangyu Meng3, Mengtao Li3, Dongwei Fan1, Tianqi Fan1, Ann Y Huang4, Zhongqiang Chen1✉, Chi Zhang3,4,5✉

1. Department of Orthopedics, Peking University Third Hospital, Beijing, China
2. Department of Orthopedics, The First Affiliated Hospital of Dalian Medical University, Dalian, China
3. Central Laboratory, Peking University International Hospital, Beijing, China
4. Bone Research Laboratory, University of Texas Southwestern Medical Center, Dallas, Texas, USA
5. Department of Orthopedics, Peking University International Hospital, Beijing, China

Abstract

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.

Keywords: thoracic ossification of the ligamentum flavum, miR-490-3p, osteogenic differentiation, FOXO1

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Yang X, Qu X, Meng X, Li M, Fan D, Fan T, Huang AY, Chen Z, Zhang C. MiR-490-3p inhibits osteogenic differentiation in thoracic ligamentum flavum cells by targeting FOXO1. Int J Biol Sci 2018; 14(11):1457-1465. doi:10.7150/ijbs.26686. Available from http://www.ijbs.com/v14p1457.htm