PMID- 31864017 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20220531 IS - 1878-5905 (Electronic) IS - 0142-9612 (Linking) VI - 231 DP - 2020 Feb TI - miR-381-abundant small extracellular vesicles derived from kartogenin-preconditioned mesenchymal stem cells promote chondrogenesis of MSCs by targeting TAOK1. PG - 119682 LID - S0142-9612(19)30781-1 [pii] LID - 10.1016/j.biomaterials.2019.119682 [doi] AB - 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. CI - Copyright (c) 2019 Elsevier Ltd. All rights reserved. FAU - Jing, Hui AU - Jing H AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Thoracic Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhang, Xiaoyang AU - Zhang X AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Luo, Kai AU - Luo K AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Luo, Qiancheng AU - Luo Q AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Yin, Meng AU - Yin M AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Wang, Wei AU - Wang W AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zhu, Zhongqun AU - Zhu Z AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. FAU - Zheng, Jinghao AU - Zheng J AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: zhengjh210@163.com. FAU - He, Xiaomin AU - He X AD - Department of Cardiothoracic Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: mrxmhe@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20191214 PL - Netherlands TA - Biomaterials JT - Biomaterials JID - 8100316 RN - 0 (Anilides) RN - 0 (MIRN381 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (Phthalic Acids) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.1 (TAO1 protein kinase) RN - Q93BBN11CP (kartogenin) SB - IM MH - Anilides MH - Cell Differentiation MH - *Chondrogenesis MH - *Extracellular Vesicles MH - Humans MH - *Mesenchymal Stem Cells MH - *MicroRNAs/genetics MH - Phthalic Acids MH - Protein Serine-Threonine Kinases/*genetics MH - Signal Transduction OTO - NOTNLM OT - Chondrogenesis OT - Kartogenin OT - Mesenchymal stem cells OT - Small extracellular vesicles OT - miRNA EDAT- 2019/12/22 06:00 MHDA- 2021/05/15 06:00 CRDT- 2019/12/22 06:00 PHST- 2019/07/08 00:00 [received] PHST- 2019/12/08 00:00 [revised] PHST- 2019/12/11 00:00 [accepted] PHST- 2019/12/22 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2019/12/22 06:00 [entrez] AID - S0142-9612(19)30781-1 [pii] AID - 10.1016/j.biomaterials.2019.119682 [doi] PST - ppublish SO - Biomaterials. 2020 Feb;231:119682. doi: 10.1016/j.biomaterials.2019.119682. Epub 2019 Dec 14.