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Long noncoding RNA expression profiles in chondrogenic and hypertrophic differentiation of mouse mesenchymal stem cells
Authors:Zhen Cao  Song Huang  Jianmei Li  Yun Bai  Ce Dou  Chuan Liu  Fei Kang  Xiaoshan Gong  Haibin Ding  Tianyong Hou  Shiwu Dong
Institution:1.Department of Biomedical Materials Science, School of Biomedical Engineering,Third Military Medical University,Chongqing,China;2.Department of Anatomy,Third Military Medical University,Chongqing,China;3.School of Pathology and Laboratory Medicine,The University of Western Australia,Nedlands,Australia;4.National & Regional United Engineering Laboratory of Tissue Engineering, Department of Orthopedics, Southwest Hospital,Third Military Medical University,Chongqing,China
Abstract:Long noncoding RNAs (lncRNAs) are important regulators for a variety of biological processes. Chondrogenic differentiation of mesenchymal stem cells (MSCs) is a crucial stage in chondrogenesis while chondrocyte hypertrophy is related to endochondral ossification and osteoarthritis. However, the effects of lncRNAs on chondrogenic and hypertrophic differentiation of mouse MSCs are unclear. To explore the potential mechanisms of lncRNAs during chondrogenesis and chondrocyte hypertrophy, microarray was performed to investigate the expression profiles of lncRNA and mRNA in MSCs, pre-chondrocytes, and hypertrophic chondrocytes. Then, we validated microarray data by RT-PCR and screened three lncRNAs from upregulating groups during chondrogenesis and chondrocyte hypertrophy respectively. After downregulating any of the above lncRNAs, we found that the expression of chondrogenesis-related genes such as Sox9 and Col2a1 and hypertrophy-related genes including Runx2 and Col10a1 was inhibited, respectively. Furthermore, the target genes of above lncRNAs were predicted by bioinformatics approaches. Gene ontology and Kyoto encyclopedia of genes and genome biological pathway analysis were also made to speculate the functions of above lncRNAs. In conclusion, the study first revealed the expression profile of lncRNAs in chondrogenic and hypertrophic differentiations of mouse MSCs and presented a new prospect for the underlying mechanisms of chondrogenesis and endochondral ossification.
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