Journal
JOURNAL OF BONE AND MINERAL RESEARCH
Volume 29, Issue 7, Pages 1575-1585Publisher
WILEY
DOI: 10.1002/jbmr.2163
Keywords
MIR-335-5P; MEST; STEM CELL; SOX9; CHONDROGENIC DIFFERENTIATION
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Funding
- National Natural Science Foundation of China [31170940, 31070095]
- State Basic Science Foundation 973 [2012CB725204]
- National High Technology Research and Development Program of China (863) [2012AA020503, 2011AA02A201, 2012AA02A700]
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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 beta-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. (C) 2014 American Society for Bone and Mineral Research.
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