title: MiR-132-3p Regulates the Osteogenic Differentiation of Thoracic Ligamentum Flavum Cells by Inhibiting Multiple Osteogenesis-Related Genes.
abstract: Ossification of the ligamentum flavum (OLF) is a disorder of heterotopic ossification of spinal ligaments and is the main cause of thoracic spinal canal stenosis. Previous studies suggested that miR-132-3p negatively regulates osteoblast differentiation. However, whether miR-132-3p is involved in the process of OLF has not been investigated. In this study, we investigated the effect of miR-132-3p and its target genes forkhead box O1 (FOXO1), growth differentiation factor 5 (GDF5) and SRY-box 6 (SOX6) on the osteogenic differentiation of ligamentum flavum (LF) cells. We demonstrated that miR-132-3p was down-regulated during the osteogenic differentiation of LF cells and negatively regulated the osteoblast differentiation. Further, miR-132-3p targeted FOXO1, GDF5 and SOX6 and down-regulated the protein expression of these genes. Meanwhile, FOXO1, GDF5 and SOX6 were up-regulated after osteogenic differentiation and the down-regulation of endogenous FOXO1, GDF5 or SOX6 suppressed the osteogenic differentiation of LF cells. In addition, we also found FOXO1, GDF5 and SOX6 expression in the ossification front of OLF samples. Overall, these results suggest that miR-132-3p inhibits the osteogenic differentiation of LF cells by targeting FOXO1, GDF5 and SOX6.
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. xiaochen13@hotmail.com.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. puth_czq@126.com.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. fdw_puth@163.com.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. scg_puth@163.com.
authors.forename: Chuiguo
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing 100191, China. zy_puth@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
mesh_terms: D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D000071161:Forkhead Box Protein O1 / Q000235:genetics; D055428:Growth Differentiation Factor 5 / Q000235:genetics; D006801:Humans; D017843:Ligamentum Flavum / Q000166:cytology* / Q000378:metabolism*; D035683:MicroRNAs / Q000235:genetics*; D010012:Osteogenesis / Q000235:genetics*; D055755:SOXD Transcription Factors / Q000235:genetics
chemical_list: D000071161:Forkhead Box Protein O1; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; C547077:MIRN132 microRNA, human; D035683:MicroRNAs; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors
keywords: FOXO1; GDF5; SOX6; miR-132-3p; ossification of the ligamentum flavum; osteogenic differentiation