miR-27a-5p-Abundant Small Extracellular Vesicles Derived From Epimedium-Preconditioned Bone Mesenchymal Stem Cells Stimulate Osteogenesis by Targeting Atg4B-Mediated Autophagy.
miR-27a-5p-Abundant Small Extracellular Vesicles Derived From Epimedium-Preconditioned Bone Mesenchymal Stem Cells Stimulate Osteogenesis by Targeting Atg4B-Mediated Autophagy.
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淫羊藿预处理的骨间充质干细胞衍生的 miR-27a-5p-丰富的小细胞外囊泡通过靶向 Atg4B 介导的自噬刺激成骨
DOI：
10.3389/fcell.2021.642646
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发表时间：
2021
影响因子：
5.5
通讯作者：
Zhang R
中科院分区：
文献类型：
--
作者：
Li X;Chen R;Li Y;Wang P;Cui Y;Yang L;Zhu X;Zhang R
骨质疏松症（OP）是一种影响老年人的疾病，其特征是渐进性骨折和骨脆性。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，我们评估了来源于淫羊藿预处理的骨髓间充质干细胞（EPI-sEV）的成骨细胞和卵巢切除（OVX）大鼠的sEV的成骨作用。通过RNA测序探索EPI-sEV诱导成骨的潜在机制，并通过用相应的模拟物和抑制剂转染来验证。EPI-sEV刺激OVX大鼠成骨细胞的成骨分化，并调节骨量和微观结构。测序鉴定了EPI-sEV中一组microRNA（miRNA）的独特富集。体外过表达或抑制表明，成骨诱导潜力主要归因于miR-27 a-5 p，其是EPI-sEV组分中最丰富的miRNA之一。双荧光素酶报告基因分析表明miR-27 a-5 p通过靶向Atg 4 B的3′非翻译区直接抑制Atg 4 B而促进成骨。另外的实验表明，miR-27 a-5 p抑制OVX大鼠中激活的自噬。此外，成骨细胞的成骨分化被雷帕霉素干预消融。这些数据报告了EPI-sEV诱导成骨细胞的成骨分化导致骨形成的再生潜力。该过程通过将sEV-miR-27 a-5 p递送至靶Atg 4 B以进一步刺激自噬来实现。
Osteoporosis (OP) is a disease affecting the elderly and is characterized by incremental fractures and bone fragility. Small extracellular vesicles (sEVs) derived from mesenchymal stem cells have been demonstrated to possess potent regeneration potential. In this study, we evaluated the osteogenesis effects of sEVs derived from Epimedium-preconditioned bone mesenchymal stem cells (EPI-sEV) from osteoblasts and ovariectomized (OVX) rats. The underlying mechanism of EPI-sEV-induced osteogenesis was explored by RNA-sequencing and verified by transfection with the corresponding mimic and inhibitor. EPI-sEV stimulated osteogenic differentiation of osteoblasts and moderated both bone mass and microstructure in OVX rats. Sequencing identified a unique enrichment of a set of microRNAs (miRNAs) in EPI-sEV. Overexpression or inhibition in vitro demonstrated that the osteogenesis-inducing potential was primarily attributed to miR-27a-5p, one of the most abundant miRNAs in the EPI-sEV fraction. Dual-luciferase reporter assays showed that miR-27a-5p promoted osteogenesis through direct suppression of Atg4B by targeting its 3′ untranslated region. Additional experiments showed that miR-27a-5p suppressed autophagy that was activated in OVX rats. Moreover, osteogenic differentiation was ablated by the intervention with rapamycin in osteoblasts. These data report the regenerative potential of EPI-sEV to induce osteogenic differentiation of osteoblast cells leading to bone formation. This process is achieved by delivering sEV-miR-27a-5p to target Atg4B for further autophagy stimulation.
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DOI：
10.1007/s00198-020-05497-8
发表时间：
2020-12
期刊：
Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA
影响因子：
--
作者：
Rozenberg S;Al-Daghri N;Aubertin-Leheudre M;Brandi ML;Cano A;Collins P;Cooper C;Genazzani AR;Hillard T;Kanis JA;Kaufman JM;Lambrinoudaki I;Laslop A;McCloskey E;Palacios S;Prieto-Alhambra D;Reginster JY;Rizzoli R;Rosano G;Trémollieres F;Harvey NC
通讯作者：
Harvey NC
影响因子：
2.1
作者：
Li, Qiushi;Li, Chen;Li, Meihua
通讯作者：
Li, Meihua
影响因子：
5.6
作者：
Li, Xiaoyun;Peng, Bojia;Yang, Li
通讯作者：
Yang, Li
影响因子：
2.4
作者：
Hu, Zhanying;Chen, Bo;Zhao, Qiong
通讯作者：
Zhao, Qiong
影响因子：
11.8
作者：
DeSelm, Carl J.;Miller, Brian C.;Zou, Wei;Beatty, Wandy L.;van Meel, Helena;Takahata, Yoshifumi;Klumperman, Judith;Tooze, Sharon A.;Teitelbaum, Steven L.;Virgin, Herbert W.
通讯作者：
Virgin, Herbert W.