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间充质干细胞外泌体来源的微小RNA-194-5p通过靶向TRAF6延缓椎间盘退变的发展。

Mesenchymal stem cell extracellular vesicles-derived microRNA-194-5p delays the development of intervertebral disc degeneration by targeting TRAF6.

作者信息

Sun Zhongyi, Tang Xiaoming, Li Qiuyuan, Wang Haibin, Sun Hongzhi, Tian Jiwei

机构信息

Department of Orthopaedics, The Affiliated BenQ Hospital of Nanjing Medical University, Nanjing 210048, Jiangsu, China.

The Affiliated Huai'an No.1 People's Hospital of Nanjing Medical University, Huaian 223300, Jiangsu, China.

出版信息

Regen Ther. 2022 Jan 20;19:88-96. doi: 10.1016/j.reth.2021.12.001. eCollection 2022 Mar.

DOI:10.1016/j.reth.2021.12.001
PMID:35127996
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8787669/
Abstract

OBJECTIVE

Mesenchymal stem cells-derived extracellular vesicles (MSCs-EVs) can improve intervertebral disc degeneration (IDD). Considering that, their concrete mechanisms from microRNA-194-5p/tumor receptor-associated factor 6 (miR-194-5p/TRAF6) axis in IDD ask for disclosure in a scientific way.

METHODS

Nucleus pulposus (NP) cells and MSCs were obtained. EVs were isolated from the obtained MSCs and identified. miR-194-5p expression in MSC-EVs was altered by sequence transfection. Subsequently, MSCs-EVs were co-cultured with NP cells intervened by tumor necrosis factor α (TNF-α). NP cell proliferation and apoptosis, along with their osteogenic differentiation ability were evaluated. miR-194-5p and TRAF6 expression and their interaction were determined.

RESULTS

In TNF-α-intervened NP cells, miR-194-5p was down-regulated and TRAF6 was up-regulated. Restoring miR-194-5p effectively enhanced proliferation and osteogenic differentiation, and reduced apoptosis of TNF-α-intervened NP cells. miR-194-5p-enriched MSCs-EVs protected TNF-α-intervened NP cells. miR-194-5p targeted TRAF6, TRAF6 overexpression exerted negatively for the growth of TNF-α-intervened NP cells, and could reduce the protective effects of miR-194-5p on TNF-α-intervened NP cells.

CONCLUSION

It is elucidated that miR-194-5p derived from MSCs-EVs protects TNF-α-intervened NP cells through restricting TRAF6, replenishing a potential target for IDD treatment.

摘要

目的

间充质干细胞衍生的细胞外囊泡（MSCs-EVs）可改善椎间盘退变（IDD）。鉴于此，其在IDD中通过微小RNA-194-5p/肿瘤受体相关因子6（miR-194-5p/TRAF6）轴发挥作用的具体机制有待科学揭示。

方法

获取髓核（NP）细胞和间充质干细胞。从获取的间充质干细胞中分离并鉴定细胞外囊泡。通过序列转染改变MSCs-EVs中miR-194-5p的表达。随后，将MSCs-EVs与经肿瘤坏死因子α（TNF-α）干预的NP细胞共培养。评估NP细胞的增殖、凋亡及其成骨分化能力。测定miR-194-5p和TRAF6的表达及其相互作用。

结果

在TNF-α干预的NP细胞中，miR-194-5p下调，TRAF6上调。恢复miR-194-5p可有效增强TNF-α干预的NP细胞的增殖和成骨分化，并减少其凋亡。富含miR-194-5p的MSCs-EVs对TNF-α干预的NP细胞具有保护作用。miR-194-5p靶向TRAF6，TRAF6过表达对TNF-α干预的NP细胞生长产生负面影响，并可降低miR-194-5p对TNF-α干预的NP细胞的保护作用。

结论

阐明了源自MSCs-EVs的miR-194-5p通过抑制TRAF6来保护TNF-α干预的NP细胞，为IDD治疗补充了一个潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/c5f2bb826d1f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/e64bf10ec46c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/9cf751e7266c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/8d7783d426d5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/56833d7b17d1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/3934e89fa97c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/c5f2bb826d1f/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/e64bf10ec46c/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/9cf751e7266c/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/8d7783d426d5/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/56833d7b17d1/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/3934e89fa97c/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c4d2/8787669/c5f2bb826d1f/gr6.jpg

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