title: MiR-335-5p promotes chondrogenesis in mouse mesenchymal stem cells and is regulated through two positive feedback loops.
abstract: Chondrogenic differentiation of mesenchymal stem cells (MSCs) is regulated by many factors and signal pathways, including transcription factors such as Sox9 and microRNAs. MiR-335-5p has been previously reported to regulate osteogenic and adipogenic differentiations of MSCs, but its role in chondrogenic differentiation of MSC remains unknown. In this study, we found that miR-335-5p and its host gene Mest are co-expressed and greatly upregulated during mouse MSCs (mMSCs) chondrogenesis. Overexpression of miR-335-5p in mMSCs increased expression of chondrogenic marker genes. Molecular mechanism explorations revealed that miR-335-5p targets Daam1 and ROCK1, a set of negative regulators of Sox9; Sox9 downregulates the expression of miR-29a and 29b, both negative regulators of Mest expression, thus forming a positive loop from miR-335-5p to Sox9 to Mest/miR-335-5p. In addition, miR-335-5p targets DKK1 during mMSC chondrogenic differentiation to increase β-catenin/TCF activity, which leads to increased level of Mest transcription. These data showed miR-335-5p positively regulates MSC chondrogenesis, and two positive feedback loops are identified for the expression of miR-335-5p and its host gene Mest during the early phase of mMSC chondrogenic differentiation.
authors.affiliation: School of Life Sciences, Tsinghua University, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Lin
authors.forename: Li
authors.initials: L
authors.lastname: Wu
authors.forename: Zhenming
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ruohuan
authors.initials: R
authors.lastname: Yang
authors.forename: Qian
authors.initials: Q
authors.lastname: Guan
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Hou
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics; D020219:Chondrogenesis / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics; D025461:Feedback, Physiological; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics; D020741:rho GTP-Binding Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C447413:Col2a1 protein, mouse; D024043:Collagen Type II; C501127:Dkk1 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; C547014:MIRN29 microRNA, mouse; D035683:MicroRNAs; D008840:Microfilament Proteins; C541986:Mirn335 microRNA, mouse; D011506:Proteins; D055758:SOX9 Transcription Factor; C103637:mesoderm specific transcript protein; C515854:Rock1 protein, mouse; D054460:rho-Associated Kinases; C500365:Daam1 protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein
keywords: CHONDROGENIC DIFFERENTIATION; MEST, STEM CELL; MIR-335-5P; SOX9