miR-483 targets SMAD4 to suppress chondrogenic differentiation of human mesenchymal stem cells.
miR-483 targets SMAD4 to suppress chondrogenic differentiation of human mesenchymal stem cells.
复制标题
miR-483靶向SMAD4以抑制人间充质干细胞的软骨分化。
DOI：
10.1002/jor.23552
复制
发表时间：
2017-11
期刊：
影响因子：
--
通讯作者：
McAlinden A
中科院分区：
文献类型：
--
作者：
Anderson BA;McAlinden A
MicroRNAs （miRNAs）可以通过同时调节多种途径来调节细胞分化过程。先前的研究分析了发育中的人肢体软骨组织中miRNA的体内表达模式，发现miR-483在肥大软骨细胞中相对于增殖和分化的软骨细胞显著下调。为了测试miR-483在软骨形成过程中的功能，我们使用慢病毒策略在人骨髓间充质干细胞（hBM-MSCs）的体外软骨形成过程中过表达miR-483。虽然体内表达模式使我们假设miR-483可能增强软骨形成或抑制增生性标志物的表达，但令人惊讶的是，miR-483过表达减少了软骨细胞基因表达和软骨基质的产生。此外，在软骨形成试验的后期诱导细胞死亡。机制研究表明，miR-483过表达导致TGF-β通路成员SMAD4下调，SMAD4是miR-483-3p的已知直接靶点。从这些研究中，我们得出结论，hBM-MSCs中miR-483的组成性过表达抑制了这些细胞的软骨形成，并且不代表一种有效的策略，试图在体外增强该系统中的软骨细胞分化和合成代谢。
MicroRNAs (miRNAs) can regulate cellular differentiation processes by modulating multiple pathways simultaneously. Previous studies to analyze in vivo miRNA expression patterns in developing human limb cartilage tissue identified significant downregulation of miR-483 in hypertrophic chondrocytes relative to proliferating and differentiated chondrocytes. To test the function of miR-483 during chondrogenesis, lentiviral strategies were used to overexpress miR-483 during in vitro chondrogenesis of human bone marrow-derived mesenchymal stem cells (hBM-MSCs). While the in vivo expression patterns led us to hypothesize that miR-483 may enhance chondrogenesis or suppress hypertrophic marker expression, surprisingly, miR-483 overexpression reduced chondrocyte gene expression and cartilage matrix production. In addition, cell death was induced at later stages of the chondrogenesis assay. Mechanistic studies revealed that miR-483 overexpression resulted in downregulation of the TGF-β pathway member SMAD4, a known direct target of miR-483-3p. From these studies, we conclude that constitutive overexpression of miR-483 in hBM-MSCs inhibits chondrogenesis of these cells and does not represent an effective strategy to attempt to enhance chondrocyte differentiation and anabolism in this system in vitro.
登录
查看更多内容
影响因子：
3.7
作者：
Jin HY;Gonzalez-Martin A;Miletic AV;Lai M;Knight S;Sabouri-Ghomi M;Head SR;Macauley MS;Rickert RC;Xiao C
通讯作者：
Xiao C
影响因子：
2.3
作者：
Díaz-Prado S;Cicione C;Muiños-López E;Hermida-Gómez T;Oreiro N;Fernández-López C;Blanco FJ
通讯作者：
Blanco FJ
影响因子：
2.8
作者：
Markway, Brandon D.;Cho, Holly;Johnstone, Brian
通讯作者：
Johnstone, Brian
影响因子：
4
作者：
Ambros, Victor
通讯作者：
Ambros, Victor
影响因子：
2.7
作者：
Lim, Joohyun;Tu, Xiaolin;Choi, Kyunghee;Akiyama, Haruhiko;Mishina, Yuji;Long, Fanxin
通讯作者：
Long, Fanxin