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- Title
MiR-335-5p Promotes Chondrogenesis in Mouse Mesenchymal Stem Cells and Is Regulated Through Two Positive Feedback Loops.
- Authors
Lin, Xiao; Wu, Li; Zhang, Zhenming; Yang, Ruohuan; Guan, Qian; Hou, Xinfeng; Wu, Qiong
- Abstract
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. © 2014 American Society for Bone and Mineral Research.
- Subjects
CHONDROGENESIS; MESENCHYMAL stem cells; MICRORNA; BONE morphogenetic proteins; ADIPOGENESIS
- Publication
Journal of Bone & Mineral Research, 2014, Vol 29, Issue 7, p1575
- ISSN
0884-0431
- Publication type
Article
- DOI
10.1002/jbmr.2163