MicroRNA-495 Inhibits Chondrogenic Differentiation in Human Mesenchymal Stem Cells by Targeting Sox9

Overview

Journal Stem Cells Dev

Date 2014 Mar 25

PMID 24654627

Citations 42

Authors

Seulgi Lee

Dong Suk Yoon

Seungil Paik

Kyoung-Mi Lee

Yeonsue Jang

Jin Woo Lee

Affiliations

Soon will be listed here.

Abstract

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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