The umbilical cord mesenchymal stem cell-derived exosomal lncRNA H19 improves osteochondral activity through miR-29b-3p/FoxO3 axis.
The umbilical cord mesenchymal stem cell-derived exosomal lncRNA H19 improves osteochondral activity through miR-29b-3p/FoxO3 axis.
复制标题
脐带间充质干细胞来源的外泌体lncRNA H19通过miR-29b-3p/FoxO3轴改善骨软骨活性
DOI：
10.1002/ctm2.255
复制
发表时间：
2021-01
影响因子：
10.6
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Yan L;Liu G;Wu X
我们之前的研究表明，来自脐带间充质干细胞（UMSCs）的外泌体lncRNA H19在骨软骨再生中起关键作用。在这项研究中，我们研究了外泌体lncRNA H19是否可以作为一种竞争性内源性RNA （ceRNA）来增强软骨细胞中的骨软骨活性。通过双荧光素酶报告基因测定、RNA拉下、RNA免疫沉淀（RIP）和荧光原位杂交（FISH）来验证miR - 29b - 3p与lncRNA H19和靶mRNA FoxO3之间的相互作用。软骨细胞用UMSC衍生的外泌体处理，高表达lncRNA H19，随后进行凋亡、迁移、衰老和基质分泌评估。通过SD大鼠软骨缺损模型，探讨lncRNA H19/miR‐29b‐3p的作用及机制。成功鉴定了UMSCs，成功提取了外泌体。外泌体表现出将lncRNA H19转移到软骨细胞的能力。机制上，外泌体lncRNA H19通过作为miR‐29b‐3p的竞争内源性海绵增强骨软骨活性，miR‐29b‐3p直接靶向FoxO3。关节内注射过表达lncRNA H19的外泌体可以促进软骨的持续修复；然而，这种效应可能被miR - 29b - 3p agomir破坏。我们的研究揭示了过度表达lncRNA H19的UMSC衍生外泌体在对抗软骨缺陷策略发展中的重要作用。体外和体内均发现外泌体H19促进软骨细胞迁移、基质分泌、细胞凋亡抑制和衰老抑制。其具体机制在于外泌体H19作为一种抑制miR - 29b - 3p的ceRNA，上调软骨细胞中的FoxO3。来源于UMSCs的外泌体表现出将lncRNA H19转移到软骨细胞的能力。体外和体内均发现外泌体H19促进软骨细胞迁移、基质分泌、细胞凋亡抑制和衰老抑制。其具体机制在于外泌体H19作为一种抑制miR - 29b - 3p的ceRNA，上调软骨细胞中的FoxO3。
Our previous study revealed that the exosomal lncRNA H19 derived from umbilical cord mesenchymal stem cells (UMSCs) plays a pivotal role in osteochondral regeneration. In this study, we investigated whether the exosomal lncRNA H19 could act as a competing endogenous RNA (ceRNA) to potentiate osteochondral activity in chondrocytes. Dual‐luciferase reporter assay, RNA pull‐down, RNA immunoprecipitation (RIP), and fluorescence in situ hybridization (FISH) were carried to verify the interaction between miR‐29b‐3p and both lncRNA H19 and the target mRNA FoxO3. Chondrocytes were treated with UMSC‐derived exosomes, which highly expressing lncRNA H19 expression, followed by apoptosis, migration, senescence, and matrix secretion assessments. An in vivo SD rat cartilage defect model was carried out to explore the role and mechanism of lncRNA H19/miR‐29b‐3p. UMSCs were successfully identified, and exosomes were successfully extracted. Exosomes exhibited the ability to transfer lncRNA H19 to chondrocytes. Mechanistically, exosomal lncRNA H19 potentiated osteochondral activity by acting as a competing endogenous sponge of miR‐29b‐3p, and miR‐29b‐3p directly targeted FoxO3. Intra‐articular injection of exosomes overexpressing lncRNA H19 could promote sustained cartilage repair; however, this effect could be undermined by miR‐29b‐3p agomir. Our study revealed a significant role in the development of strategies against cartilage defects for UMSC‐derived exosomes that overexpress lncRNA H19. Exosomal H19 was found to promote chondrocyte migration, matrix secretion, apoptosis suppression, as well as senescence suppression, both in vitro and in vivo. The specific mechanism lies in the fact that exosomal H19 acts as a ceRNA against miR‐29b‐3p to upregulate FoxO3 in chondrocytes. Exosomes derived from UMSCs exhibited the ability to transfer lncRNA H19 to chondrocytes. Exosomal H19 was found to promote chondrocyte migration, matrix secretion, apoptosis suppression, as well as senescence suppression, both in vitro and in vivo. The specific mechanism lies in the fact that exosomal H19 acts as a ceRNA against miR‐29b‐3p to upregulate FoxO3 in chondrocytes.
登录
查看更多内容
影响因子：
16
作者：
Lötvall J;Hill AF;Hochberg F;Buzás EI;Di Vizio D;Gardiner C;Gho YS;Kurochkin IV;Mathivanan S;Quesenberry P;Sahoo S;Tahara H;Wauben MH;Witwer KW;Théry C
通讯作者：
Théry C
影响因子：
17.1
作者：
Matsuzaki T;Alvarez-Garcia O;Mokuda S;Nagira K;Olmer M;Gamini R;Miyata K;Akasaki Y;Su AI;Asahara H;Lotz MK
通讯作者：
Lotz MK
DOI：
10.2106/00004623-200300002-00007
发表时间：
2003-01-01
影响因子：
5.3
作者：
Mainil-Varlet, P;Aigner, T;Stauffer, E
通讯作者：
Stauffer, E
影响因子：
5.6
作者：
Chen, Zhilan;Wei, Huafang;Zhang, Qinghua
通讯作者：
Zhang, Qinghua
双层聚丙交酯乙交酯共聚物多孔支架植入兔关节12周和24周修复骨软骨缺损
影响因子：
6.6
作者：
Duan, Pingguo;Pan, Zhen;Ding, Jiandong
通讯作者：
Ding, Jiandong