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环状 RNA 三功能域通过调节 microRNA-136-5p/烟酰胺磷酸核糖基转移酶轴促进骨关节炎的发展。

Circular RNA triple functional domain promotes osteoarthritis' development by modulating the microRNA-136-5p/Nicotinamide phosphoribosyltransferase axis.

机构信息

Department of Orthopedics, Affiliated Hospital of Shaanxi University of Chinese Medicine, Xianyang, Shaanxi Province, China.

出版信息

Bioengineered. 2022 Mar;13(3):6070-6079. doi: 10.1080/21655979.2021.2018095.

DOI:10.1080/21655979.2021.2018095
PMID:35191807
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8973697/
Abstract

Numerous studies have affirmed the participation of circular RNA (circRNA) in osteoarthritis (OA)' development. Previous studies have exposed the elevation of the circRNA triple functional domain (TRIO) in OA, while the molecular mechanism of its effect on OA remains ambiguous. During the study, it was discovered the up-regulation of circTRIO in OA rats and interleukin-1β-treated chondrocytes. Knockdown circTRIO facilitates chondrocyte viability, but suppresses the inflammation, the apoptosis, and matrix metalloproteinases (MMP)-3 and MMP-13 expression, whereas up-regulation aggravates OA. The effect of up-regulation or under-expression of circTRIO on chondrocytes was reversed via the knockdown of Nicotinamide phosphoribosyltransferase (NAMPT) or microRNA (miR)-136-5p separately. Mechanically speaking, circTRIO competitively adsorbing miR-136-5p to target NAMPT influences OA. Briefly, the results of this study inform that the circTRIO/miR-136-5p/NAMPT axis is momentous in OA progression and is supposed to be a promising therapeutic target for some time.

摘要

大量研究证实环状 RNA(circRNA)参与骨关节炎(OA)的发生。先前的研究已经揭示了 OA 中环三功能域(TRIO)的升高,但其对 OA 的影响的分子机制尚不清楚。在研究中,发现 OA 大鼠和白细胞介素 1β处理的软骨细胞中 circTRIO 的上调。circTRIO 的下调促进软骨细胞活力,但抑制炎症、凋亡和基质金属蛋白酶(MMP)-3 和 MMP-13 的表达,而上调则加重 OA。通过分别敲低烟酰胺磷酸核糖转移酶(NAMPT)或 microRNA(miR)-136-5p,circTRIO 对软骨细胞的上调或下调的作用被逆转。从机制上讲,circTRIO 竞争性吸附 miR-136-5p 以靶向 NAMPT 影响 OA。简而言之,本研究结果表明,circTRIO/miR-136-5p/NAMPT 轴在 OA 进展中具有重要意义,并且在一段时间内有望成为有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/2c4e3f8ac3d2/KBIE_A_2018095_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/9de3a5ca86e2/KBIE_A_2018095_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/31e0e6b74d4e/KBIE_A_2018095_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/59459dd01a61/KBIE_A_2018095_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/efb8fa8c8c2f/KBIE_A_2018095_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/7fb368e7f592/KBIE_A_2018095_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/2c4e3f8ac3d2/KBIE_A_2018095_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/9de3a5ca86e2/KBIE_A_2018095_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/31e0e6b74d4e/KBIE_A_2018095_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/59459dd01a61/KBIE_A_2018095_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/efb8fa8c8c2f/KBIE_A_2018095_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/7fb368e7f592/KBIE_A_2018095_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b08/8973697/2c4e3f8ac3d2/KBIE_A_2018095_F0006_OC.jpg

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