Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis.
Small extracellular vesicles in combination with sleep-related circRNA3503: A targeted therapeutic agent with injectable thermosensitive hydrogel to prevent osteoarthritis.
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小细胞外囊泡与睡眠相关的 circRNA3503 相结合：一种具有可注射热敏水凝胶的靶向治疗剂，可预防骨关节炎
DOI：
10.1016/j.bioactmat.2021.04.031
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发表时间：
2021-12
影响因子：
18.9
通讯作者：
Guo SC
中科院分区：
文献类型：
--
作者：
Tao SC;Huang JY;Gao Y;Li ZX;Wei ZY;Dawes H;Guo SC
骨关节炎（Osteoarthritis，OA）是一种以软骨细胞凋亡和细胞外基质（extracellular matrix，ECM）平衡紊乱为特征的常见的年龄相关性退行性关节病。由于已发现睡眠有利于软骨修复，并且已证明环状RNA（circRNA）参与OA的发病机制，我们进行了RNA测序（RNA-seq），发现在褪黑激素（MT）诱导的细胞睡眠后，circRNA 3503显著增加。circRNA 3503表达的上调完全挽救了用于模拟OA的白细胞介素-1 β（IL-1β）对细胞凋亡、ECM降解和合成相关基因的影响。在机制上，circRNA 3503充当hsa-miR-181 c-3 p和hsa-let-7 b-3 p的海绵。此外，正如我们先前所示，来自滑膜间充质干细胞（SMSC）的小细胞外囊泡（sEV）不仅可以成功地将核酸递送到软骨细胞，而且还可以有效地促进软骨细胞增殖和迁移，我们评估了sEV与睡眠相关的circRNA 3503组合作为OA治疗的可行性。我们成功地从SMSC中产生并分离了负载circRNA 3503的sEV（circRNA 3503-OE-sEV）。然后，使用聚（D，l-丙交酯）-b-聚（乙二醇）-b-聚（D，l-丙交酯）（PDLLA-PEG-PDLLA，PLEL）三嵌段共聚物凝胶作为sEV的载体。通过体内和体外实验，PLEL@circRNA3503-OE-sEV被证明是预防OA进展的高效治疗策略。通过多种途径，circRNA 3503-OE-sEVs通过充当hsa-miR-181 c-3 p和hsa-let-7 b-3 p的海绵来减轻炎症诱导的细胞凋亡以及ECM合成和ECM降解之间的失衡。此外，circRNA 3503-OE-sEV促进软骨细胞更新以减轻软骨细胞的进行性损失。我们的结果强调了PLEL@circRNA3503-OE-sEV预防OA进展的潜力。CircRNA 3503可减轻细胞凋亡和ECM合成与降解之间的失衡。由sEV携带的Wnt 5a/B促进软骨细胞更新以减轻软骨细胞的进行性损失。PDLLA-PEG-PDLLA（PLEL）三嵌段共聚物凝胶在sEV的缓释中显示出良好的性能。PLEL@circRNA3503-OE-sEV显示出预防OA进展的潜力。
Osteoarthritis (OA), characterized by chondrocyte apoptosis and disturbance of the balance between catabolism and anabolism of the extracellular matrix (ECM), is the most common age-related degenerative joint disease worldwide. As sleep has been found to be beneficial for cartilage repair, and circular RNAs (circRNAs) have been demonstrated to be involved in the pathogenesis of OA, we performed RNA sequencing (RNA-seq), and found circRNA3503 was significantly increased after melatonin (MT)-induced cell sleep. Upregulation of circRNA3503 expression completely rescued the effects of interleukin-1β (IL-1β), which was used to simulate OA, on apoptosis, ECM degradation- and synthesis-related genes. Mechanistically, circRNA3503 acted as a sponge of hsa-miR-181c-3p and hsa-let-7b-3p. Moreover, as we previously showed that small extracellular vesicles (sEVs) derived from synovium mesenchymal stem cells (SMSCs) can not only successfully deliver nucleic acids to chondrocytes, but also effectively promote chondrocyte proliferation and migration, we assessed the feasibility of sEVs in combination with sleep-related circRNA3503 as an OA therapy. We successfully produced and isolated circRNA3503-loaded sEVs (circRNA3503-OE-sEVs) from SMSCs. Then, poly(D,l-lactide)-b-poly(ethylene glycol)-b-poly(D,l-lactide) (PDLLA-PEG-PDLLA, PLEL) triblock copolymer gels were used as carriers of sEVs. Through in vivo and in vitro experiments, PLEL@circRNA3503-OE-sEVs were shown to be a highly-effective therapeutic strategy to prevent OA progression. Through multiple pathways, circRNA3503-OE-sEVs alleviated inflammation-induced apoptosis and the imbalance between ECM synthesis and ECM degradation by acting as a sponge of hsa-miR-181c-3p and hsa-let-7b-3p. In addition, circRNA3503-OE-sEVs promoted chondrocyte renewal to alleviate the progressive loss of chondrocytes. Our results highlight the potential of PLEL@circRNA3503-OE-sEVs for preventing OA progression. CircRNA3503 alleviated apoptosis and the imbalance between ECM synthesis and ECM degradation. Wnt5a/b carried by sEVs promoted chondrocyte renewal to alleviate the progressive loss of chondrocytes. PDLLA-PEG-PDLLA (PLEL) triblock copolymer gels showed good performance in slow release of sEVs. PLEL@circRNA3503-OE-sEVs showed potential to prevent OA progression.
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DOI：
10.1007/s40883-019-00109-2
发表时间：
2019-09-01
影响因子：
2.6
作者：
Diaz-Rodriguez, Patricia;Erndt-Marino, Josh;Hahn, Mariah S.
通讯作者：
Hahn, Mariah S.
环状RNA VMA21通过靶向miR-200c和X连锁凋亡抑制剂蛋白来防止椎间盘退变
影响因子：
27.4
作者：
Cheng X;Zhang L;Zhang K;Zhang G;Hu Y;Sun X;Zhao C;Li H;Li YM;Zhao J
通讯作者：
Zhao J
影响因子：
4.8
作者：
Feng, Ye;Liang, Yan;Dai, Chunsun
通讯作者：
Dai, Chunsun
影响因子：
64.5
作者：
Farez MF;Mascanfroni ID;Méndez-Huergo SP;Yeste A;Murugaiyan G;Garo LP;Balbuena Aguirre ME;Patel B;Ysrraelit MC;Zhu C;Kuchroo VK;Rabinovich GA;Quintana FJ;Correale J
通讯作者：
Correale J
影响因子：
4
作者：
Iannone, F;Lapadula, G
通讯作者：
Lapadula, G