MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9.
MicroRNA-145 regulates chondrogenic differentiation of mesenchymal stem cells by targeting Sox9.
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MicroRNA-145 通过靶向 Sox9 调节间充质干细胞的软骨分化
DOI：
10.1371/journal.pone.0021679
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Dong S
中科院分区：
文献类型：
--
作者：
Yang B;Guo H;Zhang Y;Chen L;Ying D;Dong S
间充质干细胞（MSCs）的软骨分化是由重要的转录因子和信号级联精确调控的。然而，这一过程所涉及的确切机制仍有待确定。microRNAs（miRNAs）通过与靶mRNA结合来抑制蛋白质合成，从而调控多种生物学过程。为了研究miRNA介导的软骨分化调节机制，我们确定了在转化生长因子β 3（TGF-β3）诱导的小鼠MSC软骨分化过程中miR-145减少。随后，双荧光素酶报告基因分析数据表明，miR-145靶向SRY相关的高迁移率族盒基因9（Sox 9）基因3′-UTR中的一个假定结合位点，该基因是软骨形成的关键转录因子。此外，miR-145的过表达仅在蛋白水平上降低Sox 9的表达，而miR-145抑制显著升高Sox 9蛋白水平。此外，miR-145过表达可降低TGF-β3诱导的C3 H10 T1/2细胞中II型胶原（Col 2a 1）、聚集蛋白聚糖（Agc 1）、软骨寡聚基质蛋白（COMP）、IX型胶原（Col 9a 2）和XI型胶原（Col 11 a1）3种软骨形成标志基因的mRNA水平，而抗miR-145抑制剂可增加这些软骨形成标志基因的表达。因此，我们的研究表明，miR-145是软骨分化的关键负调控因子，在软骨分化的早期阶段直接靶向Sox 9。
Chondrogenic differentiation of mesenchymal stem cells (MSCs) is accurately regulated by essential transcription factors and signaling cascades. However, the precise mechanisms involved in this process still remain to be defined. MicroRNAs (miRNAs) regulate various biological processes by binding target mRNA to attenuate protein synthesis. To investigate the mechanisms for miRNAs-mediated regulation of chondrogenic differentiation, we identified that miR-145 was decreased during transforming growth factor beta 3 (TGF-β3)-induced chondrogenic differentiation of murine MSCs. Subsequently, dual-luciferase reporter gene assay data demonstrated that miR-145 targets a putative binding site in the 3′-UTR of SRY-related high mobility group-Box gene 9 (Sox9) gene, the key transcription factor for chondrogenesis. In addition, over-expression of miR-145 decreased expression of Sox9 only at protein levels and miR-145 inhibition significantly elevated Sox9 protein levels. Furthermore, over-expression of miR-145 decreased mRNA levels for three chondrogenic marker genes, type II collagen (Col2a1), aggrecan (Agc1), cartilage oligomeric matrix protein (COMP), type IX collagen (Col9a2) and type XI collagen (Col11a1) in C3H10T1/2 cells induced by TGF-β3, whereas anti-miR-145 inhibitor increased the expression of these chondrogenic marker genes. Thus, our studies demonstrated that miR-145 is a key negative regulator of chondrogenic differentiation by directly targeting Sox9 at early stage of chondrogenic differentiation.
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影响因子：
64.8
作者：
Cordes KR;Sheehy NT;White MP;Berry EC;Morton SU;Muth AN;Lee TH;Miano JM;Ivey KN;Srivastava D
通讯作者：
Srivastava D
DOI：
10.1073/pnas.0407510102
发表时间：
2005-02-15
影响因子：
11.1
作者：
Kawakami, Y;Tsuda, M;Asahara, H
通讯作者：
Asahara, H
影响因子：
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作者：
Ikeda, T;Kamekura, S;Chung, UI
通讯作者：
Chung, UI
DOI：
10.1073/pnas.0800650105
发表时间：
2008-07-01
影响因子：
11.1
作者：
Kong, Yi Wen;Cannell, Ian G.;Bushell, Martin
通讯作者：
Bushell, Martin
DOI：
10.1016/j.biocel.2008.10.032
发表时间：
2009-05
影响因子：
4
作者：
Furumatsu, Takayuki;Ozaki, Toshifumi;Asahara, Hiroshi
通讯作者：
Asahara, Hiroshi