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

Seulgi Lee, Dong Suk Yoon, Seungil Paik, Kyoung Mi Lee, Yeonsue Jang, jinwoo lee

Research output: Contribution to journalArticle

44 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1798-1808
Number of pages11
JournalStem Cells and Development
Volume23
Issue number15
DOIs
Publication statusPublished - 2014 Aug 1

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MicroRNAs
Mesenchymal Stromal Cells
3' Untranslated Regions
Aggrecans
Collagen Type II
Extracellular Matrix Proteins
Transforming Growth Factors
Proteoglycans
Luciferases
Real-Time Polymerase Chain Reaction
Cell Differentiation
Seeds
Down-Regulation
Binding Sites

All Science Journal Classification (ASJC) codes

  • Hematology
  • Developmental Biology
  • Cell Biology

Cite this

Lee, Seulgi ; Yoon, Dong Suk ; Paik, Seungil ; Lee, Kyoung Mi ; Jang, Yeonsue ; lee, jinwoo. / MicroRNA-495 Inhibits chondrogenic differentiation in human mesenchymal stem cells by targeting Sox9. In: Stem Cells and Development. 2014 ; Vol. 23, No. 15. pp. 1798-1808.
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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, jinwoo.

In: Stem Cells and Development, Vol. 23, No. 15, 01.08.2014, p. 1798-1808.

Research output: Contribution to journalArticle

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