miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1
miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1
复制标题
来自kartogenin预处理的间充质干细胞的富含miR-381的小细胞外囊泡通过靶向TAOK1促进MSC的软骨形成
DOI：
10.1016/j.biomaterials.2019.119682
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发表时间：
2020-02-01
期刊：
影响因子：
14
通讯作者：
He, Xiaomin
中科院分区：
文献类型：
--
作者：
Jing, Hui;Zhang, Xiaoyang;He, Xiaomin
来源于间充质干细胞的小细胞外囊泡（sEV）已被证明具有强大的再生潜力。在这项研究中，我们评估了来自kartogenin预处理的人脐带间充质干细胞（hUCMSCs）的sEV的软骨形成作用。通过梯度超速离心从KGN预处理的hUCMSCs（KGN-sEV）的上清液中分离sEV，并被天然hUCMSCs内化，从而诱导软骨分化。通过高通量测序探索KGN-sEV诱导软骨形成的潜在机制，并通过用相应的模拟物和抑制剂转染来验证。测序鉴定了KGN-sEV中一组miRNA与来自未预处理细胞的sEV（un-sEV）相比的独特富集。体外和体内的过表达/抑制表明，这种软骨形成诱导潜力主要归因于miR-381- 3 p，其是KGN-sEV中最丰富的miRNA之一。双荧光素酶报告基因分析显示，miR-381- 3 p通过靶向TAOK 1的3'非翻译区直接抑制TAOK 1，从而抑制Hippo信号通路，从而促进软骨形成。总的来说，我们的结果突出了KGN-sEV诱导MSC软骨分化的再生潜力，这主要是通过递送靶向TAOK 1的sEV-miR-381- 3 p来实现的。
Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have been shown to possess potent regenerative potential. In this study, we evaluated the chondrogenic effect of sEVs derived from kartogenin-preconditioned human umbilical cord mesenchymal stem cells (hUCMSCs). sEVs were isolated from the supernatants of KGN-preconditioned hUCMSCs (KGN-sEV) by gradient ultra-centrifugation, and internalized by native hUCMSCs, thereby inducing the chondrogenic differentiation. The underlying mechanism of KGN-sEV-induced chondrogenesis was explored by high-throughput sequencing and verified by transfection with the corresponding mimic and inhibitor. Sequencing identified the unique enrichment of a set of miRNAs in KGN-sEV compared with sEVs derived from unpreconditioned cells (un-sEV). Overexpression/inhibition in vitro and in vivo demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-381-3p, one of the most abundant miRNAs in KGN-sEV. Dual-luciferase reporter assays showed that miR-381-3p promoted chondrogenesis through direct suppression of TAOK1 by targeting its 3' untranslated region, thereby suppressing the Hippo signaling pathway. Collectively, our results highlight the regenerative potential of KGN-sEV to induce chondrogenic differentiation of MSCs, which is mainly achieved by delivering sEV-miR-381-3p, which targets TAOK1.