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lncRNA ADAMTS9-AS2 Controls Human Mesenchymal Stem Cell Chondrogenic Differentiation and Functions as a ceRNA

Ming-Jian Huang, Jing-Yu Zhao, Jia-Jia Xu, Jing Li, Yi-Fu Zhuang, Sciprofile linkXiao-Ling Zhang
Published: 1 December 2019
Molecular Therapy - Nucleic Acids , Volume 18, pp 533-545; doi:10.1016/j.omtn.2019.08.027

Abstract: Long noncoding RNAs (lncRNAs) have emerged as key regulators of cell differentiation and development. However, potential roles for lncRNAs in chondrogenic differentiation have remained poorly understood. Here we identify lncRNA ADAMTS9 antisense RNA 2, ADAMTS9-AS2, which controls the chondrogenic differentiation by acting as a competing endogenous RNA (ceRNA) in human mesenchymal stem cells (hMSCs). We screen out ADAMTS9-AS2 of undifferentiated and differentiated cells during chondrogenic differentiation by microarrays. Suppression or overexpression of lncRNA ADAMTS9-AS2 correlates with inhibition and promotion of hMSC chondrogenic differentiation, respectively. We find that ADAMTS9-AS2 can sponge miR-942-5p to regulate the expression of Scrg1, a transcription factor promoting chondrogenic gene expression. Finally, we confirm the function of ADAMTS9-AS2 to cartilage repair in the absence of transforming growth factor β (TGF-β) in vivo. In conclusion, ADAMTS9-AS2 plays an important role in chondrogenic differentiation as a ceRNA, so that it can be regarded as a therapy target for cartilage repair.
Keywords: LncRNA ADAMTS9-AS2; MiR-942-5p; chondrogenesis; hMSCs; cartilage regeneration; chondrogenic differentiation; cartilage defect

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