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MicroRNA-495 Inhibits chondrogenic differentiation in human mesenchymal stem cells by targeting Sox9

 Lee Seulgi  ;  Yoon Dong Suk  ;  Paik Seungil  ;  Lee Kyoung-Mi  ;  Jang Yeonsue  ;  Lee Jin Woo 
 STEM CELLS AND DEVELOPMENT, Vol.23(15) : 1798-1808, 2014 
Journal Title
Issue Date
3' Untranslated Regions/genetics ; Adult ; Base Sequence ; Biomarkers/metabolism ; Cell Differentiation/drug effects ; Cell Differentiation/genetics* ; Cell Line, Tumor ; Cell Lineage/drug effects ; Cell Lineage/genetics ; Cells, Cultured ; Chondrogenesis/drug effects ; Chondrogenesis/genetics* ; Gene Expression Regulation/drug effects ; Glycosaminoglycans/metabolism ; Humans ; Immunohistochemistry ; Mesenchymal Stromal Cells/cytology* ; Mesenchymal Stromal Cells/drug effects ; Mesenchymal Stromal Cells/metabolism ; MicroRNAs/genetics ; MicroRNAs/metabolism* ; Middle Aged ; Molecular Sequence Data ; Protein Binding/drug effects ; Protein Binding/genetics ; Proteoglycans/metabolism ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; SOX9 Transcription Factor/genetics* ; SOX9 Transcription Factor/metabolism ; Transforming Growth Factor beta3/pharmacology ; Young Adult
The chondrogenic differentiation process of human mesenchymal stem cells (hMSCs) passes through multiple stages, which are carried out by various factors and their interactions. Recently, microRNAs that regulate chondrogenic differentiation have been reported. However, microRNA that regulates SRY-related high mobility group-box gene 9 (Sox9), a chondrogenic key factor, has not been identified in hMSC. In this study, we identified that microRNA-495 (miR-495) is an important regulator of hMSC chondrogenic differentiation. In our microarray, miR-495 was downregulated during transforming growth factor (TGF)-β3-induced chondrogenic differentiation of hMSCs in vitro. We found that there is an miR-495 binding site in the 3′ untranslated region (3′UTR) of Sox9. We confirmed opposite expression between miR-495 and Sox9 by using real-time polymerase chain reaction. Further, overexpression of miR-495 inhibited Sox9 expression, and repression of miR-495 increased expression of Sox9 in SW1353 cells and hMSCs. Additionally, luciferase analysis revealed that miR-495 directly binds to the Sox9 3′UTR, and we confirmed a seed sequence of miR-495 on the Sox9 3′UTR. Subsequently, overexpression of miR-495 repressed the expression of the extracellular matrix (ECM) protein, such as type II collagen (Col2A1), aggrecan, and proteoglycan products, whereas inhibition of miR-495 increased their expression. Collectively, this study indicates that miR-495 directly targets Sox9, ultimately leading to the regulation of chondrogenic differentiation in hMSCs.
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Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
Yonsei Authors
Paik, Seung Il(백승일)
Yoon, Dong Suk(윤동석)
Lee, Kyoung Mi(이경미) ORCID logo https://orcid.org/0000-0002-9038-8162
Lee, Seul Gi(이슬기)
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
Jang, Yeon Sue(장연수) ORCID logo https://orcid.org/0000-0001-5683-0001
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