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滑膜和滑液中miR-519d-3p水平降低,通过靶向血管内皮生长因子(VEGF)促进创伤后骨关节炎的进展。

Reduced miR-519d-3p levels in the synovium and synovial fluid facilitate the progression of post-traumatic osteoarthritis by targeting VEGF.

作者信息

Gao Jianlong, Xia Silong

机构信息

Department of Orthopedics, The Affiliated Jianhu Hospital of Nantong University, Yancheng, Jiangsu 224700, P.R. China.

出版信息

Exp Ther Med. 2021 Dec;22(6):1478. doi: 10.3892/etm.2021.10913. Epub 2021 Oct 25.

Abstract

The present study aimed to investigate the expression and clinical significance of miR-519d-3p in patients with post-traumatic osteoarthritis (PTOA). The levels of miR-519d-3p in the synovium and synovial fluid (SF) of all subjects were detected by reverse transcription-quantitative polymerase chain reaction. The results of the present study demonstrated that the levels of miR-519d-3p in the synovium and SF of patients with PTOA were significantly lower, but that the VEGF content was significantly higher, compared with that of control group. Dual-luciferase reporter and Western blot assays demonstrated that VEGF was a target gene of miR-519d-3p. Furthermore, miR-519d-3p inhibitor-induced cell apoptosis, and cell cycle arrest could be partially reversed by silencing VEGF. Additionally, the level of miR-519d-3p in the synovium and SF of patients with PTOA was negatively correlated with the level of VEGF. ROC analysis demonstrated that miR-519d-3p levels in the synovium and SF could effectively differentiate patients with PTOA from healthy controls, with areas under the ROC curve of 0.928 and 0.896, respectively. In conclusion, reduction of miR-519d-3p in the synovium and SF resulted in the upregulation of VEGF in patients with PTOA, and miR-519d-3p may be a potential therapeutic target of PTOA.

摘要

本研究旨在探讨miR-519d-3p在创伤后骨关节炎(PTOA)患者中的表达及其临床意义。采用逆转录-定量聚合酶链反应检测所有受试者滑膜和滑液(SF)中miR-519d-3p的水平。本研究结果表明,与对照组相比,PTOA患者滑膜和SF中miR-519d-3p水平显著降低,但血管内皮生长因子(VEGF)含量显著升高。双荧光素酶报告基因和蛋白质免疫印迹分析表明,VEGF是miR-519d-3p的靶基因。此外,miR-519d-3p抑制剂诱导的细胞凋亡和细胞周期阻滞可通过沉默VEGF而部分逆转。另外,PTOA患者滑膜和SF中miR-519d-3p水平与VEGF水平呈负相关。ROC分析表明,滑膜和SF中miR-519d-3p水平可有效区分PTOA患者与健康对照者,ROC曲线下面积分别为0.928和0.896。综上所述,PTOA患者滑膜和SF中miR-519d-3p水平降低导致VEGF上调,miR-519d-3p可能是PTOA的潜在治疗靶点。

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