The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling
The role of microRNA-23b in the differentiation of MSC into chondrocyte by targeting protein kinase A signaling
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DOI：
10.1016/j.biomaterials.2012.03.025
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发表时间：
2012-06-01
期刊：
影响因子：
14
通讯作者：
Hwang, Ki-Chul
中科院分区：
文献类型：
--
作者：
Ham, Onju;Song, Byeong-Wook;Hwang, Ki-Chul
间充质干细胞（MSCs）的软骨分化是软骨再生成功的关键。由于软骨分化细胞可以形成稳定的软骨并诱导软骨特异性表型的表达，因此已经开发了几种方法来尝试软骨分化。在本研究中，我们发现H-89和microRNA-23b均通过下调蛋白激酶A （PKA）信号通路诱导hMSCs向软骨细胞分化。小分子H-89被PCA分析鉴定为软骨分化的潜在介质。H-89诱导软骨细胞标志物aggrecan和miR-23b的表达。我们搜索miR-23b调节PKA蛋白水平。将miR-23b转染到hMSCs中，诱导成软骨分化。我们通过报告基因检测确认了miR-23b的靶标。此外，除了H-89或miR-23b处理的细胞外，H-89和miR-23b共同处理的细胞也分化为软骨细胞。我们的研究结果表明，H-89诱导内源性miR-23b的表达，从而通过负性抑制PKA信号传导诱导软骨分化。(C) 2012 Elsevier Ltd.版权所有。
Chondrogenic differentiation of mesenchymal stem cells (MSCs) is critical for successful cartilage regeneration. Several methods have been developed to attempt to chondrogenic differentiation, because chondrogenic differentiated cells can form stable cartilage and induce expression of a cartilage-specific phenotype. In this study, we found that both H-89 and microRNA-23b induced differentiation into chondrocyte of hMSCs through down-regulation of protein kinase A (PKA) signaling. The small molecule, H-89, was identified by PCA analysis as a potential mediator of chondrogenic differentiation. H-89 induced the expression of the chondrocyte marker, aggrecan, as well as miR-23b. We searched that miR-23b regulates protein level of PKA. When miR-23b was transfected into hMSCs, chondrogenic differentiation was induced. We confirmed the target of miR-23b using a reporter gene assay. Furthermore, not only H-89 or miR-23b-treated cells, but also cell co-treated with H-89 and miR-23b differentiated into chondrocytes. Our results indicate that H-89 induces the expression of endogenous miR-23b, thereby inducing chondrogenic differentiation by negatively inhibition of PKA signaling. (C) 2012 Elsevier Ltd. All rights reserved.