title: MiR-199b-5p inhibits osteogenic differentiation in ligamentum flavum cells by targeting JAG1 and modulating the Notch signalling pathway.
abstract: Ossification of the ligamentum flavum (OLF) is a pathology almost only reported in East Asian countries. The leading cause of OLF is thoracic spinal canal stenosis and myelopathy. In this study, the role of miR-199b-5p and jagged 1 (JAG1) in primary ligamentum flavum cell osteogenesis was examined. MiR-199b-5p was found to be down-regulated during osteogenic differentiation in ligamentum flavum cells, while miR-199b-5p overexpression inhibited osteogenic differentiation. In addition, JAG1 was found to be up-regulated during osteogenic differentiation in ligamentum flavum cells, while JAG1 knockdown via RNA interference caused an inhibition of Notch signalling and osteogenic differentiation. Moreover, target prediction analysis and dual luciferase reporter assays supported the notion that JAG1 was a direct target of miR-199b-5p, with miR-199b-5p found to down-regulate both JAG1 and Notch. Further, JAG1 knockdown was demonstrated to block the effect of miR-199b-5p inhibition. These findings imply that miR-199b-5p performs an inhibitory role in osteogenic differentiation in ligamentum flavum cells by potentially targeting JAG1 and influencing the Notch signalling pathway.
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Qu
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Zhongqiang
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Fan
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Chuiguo
authors.initials: C
authors.lastname: Sun
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Zhaoqing
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Qi
authors.affiliation: Department of Orthopaedics, Peking University Third Hospital, Beijing, China.
authors.forename: Weishi
authors.initials: W
authors.lastname: Li
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D000072100:Jagged-1 Protein / Q000235:genetics*; D017843:Ligamentum Flavum / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009999:Ossification, Heterotopic / Q000235:genetics* / Q000473:pathology; D010012:Osteogenesis / Q000235:genetics*; D051880:Receptors, Notch / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D035683:MicroRNAs; D051880:Receptors, Notch; C531408:mirn199 microRNA, human
keywords: JAG1; Notch signalling pathway; miR-199b-5p; ossification of the ligamentum flavum; osteogenic differentiation