lncRNA TSIX在骨关节炎发病机制中的作用:机理认识和临床生物标记潜力。

IF 2.8 3区 医学 Q1 ORTHOPEDICS
Liangchao Dong, Futao Ji, Xiu-Quan Guo, Gang-Gang Wang, Junhui Xie
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引用次数: 0

摘要

背景:本研究旨在阐明lncRNA TSIX在骨关节炎(OA)中的表达并探索其调控OA进展的机制:本研究旨在阐明lncRNA TSIX在骨关节炎(OA)中的表达,并探讨其调控OA进展的机制:方法:采用RT-qPCR分析TSIX在按Kellgren-Lawrence(K-L)分级的OA患者中的表达。方法:采用 RT-qPCR 分析按 Kellgren-Lawrence (K-L) 分级的 OA 患者中 TSIX 的表达情况,并采用接收运算特征(ROC)评估 TSIX 的诊断价值。采用皮尔逊法评估了TSIX水平与临床评分(如Lysholm和视觉模拟量表(VAS)评分)之间的相关性。IL-1β诱导的SW1353细胞作为体外模型。细胞功能通过流式细胞术和细胞计数试剂盒-8(CCK-8)检测进行评估。通过荧光素酶报告系统验证了TSIX与miR-320a之间的关系,并利用生物信息学方法预测了miR-320a的下游靶基因:结果:研究结果显示,与对照组相比,OA 患者的 TSIX 水平升高,且 TSIX 的表达与 K-L 分级的升高相关。在 OA 患者中,Lysholm 评分与 TSIX 表达呈负相关,而 VAS 评分与 TSIX 水平呈正相关。细胞研究表明,抑制 TSIX 除了能促进 Aggrecan 和胶原蛋白 II 的分泌外,还能通过靶向 miR-320a 提高细胞活力,减轻 IL-1β 诱导的细胞凋亡。荧光素酶报告实验进一步验证了 TSIX、miR-320a 和 PTEN 之间的靶向相互作用:本研究表明,TSIX 在 OA 患者中的表达量增加。结论:该研究表明 TSIX 在 OA 患者中的表达增加,这表明 TSIX 可能通过调节 miR-320a/PTEN 轴在 OA 期间软骨细胞功能障碍中发挥作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The role of lncRNA TSIX in osteoarthritis pathogenesis: mechanistic insights and clinical biomarker potential.

Background: This study seeks to elucidate the expressions of lncRNA TSIX in Osteoarthritis (OA) and to explore its mechanisms in regulating OA progression.

Methods: RT-qPCR was employed to analyze the expression of TSIX in OA patients classified by Kellgren-Lawrence (K-L) grades. Receiver operator characteristic (ROC) was conducted to evaluate the diagnostic value of TSIX. Correlation between TSIX levels and clinical scores such as Lysholm and visual analogue scale (VAS) score was evaluated using Pearson method. IL-1β-induced SW1353 cells served as an in vitro model. The cell function were assessed by flow cytometry and cell counting kit-8 (CCK-8) assay. The relationship between TSIX and miR-320a was verified by luciferase reporting system, while bioinformatics approaches were utilized to predict the downstream target genes of miR-320a.

Results: The findings revealed that TSIX level in OA patients was elevated compared to that of the control group, with a notable progressive increase in TSIX expression correlated with higher K-L grades. In OA patients, the Lysholm score showed a negative correlation with TSIX expression, while the VAS score displayed a positive correlation with TSIX levels. Cell studies demonstrated that inhibition of TSIX enhanced cell viability and mitigated IL-1β-induced apoptosis by targeting miR-320a, in addition to promoting Aggrecan and Collagen II secretion. Luciferase reporter assay further validated the targeting interaction among TSIX, miR-320a, and PTEN.

Conclusions: This study demonstrated an increased expression of TSIX in OA patients. It suggests that TSIX may play a role in chondrocyte dysfunction during OA by modulating the miR-320a/PTEN axis.

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来源期刊
CiteScore
4.10
自引率
7.70%
发文量
494
审稿时长
>12 weeks
期刊介绍: Journal of Orthopaedic Surgery and Research is an open access journal that encompasses all aspects of clinical and basic research studies related to musculoskeletal issues. Orthopaedic research is conducted at clinical and basic science levels. With the advancement of new technologies and the increasing expectation and demand from doctors and patients, we are witnessing an enormous growth in clinical orthopaedic research, particularly in the fields of traumatology, spinal surgery, joint replacement, sports medicine, musculoskeletal tumour management, hand microsurgery, foot and ankle surgery, paediatric orthopaedic, and orthopaedic rehabilitation. The involvement of basic science ranges from molecular, cellular, structural and functional perspectives to tissue engineering, gait analysis, automation and robotic surgery. Implant and biomaterial designs are new disciplines that complement clinical applications. JOSR encourages the publication of multidisciplinary research with collaboration amongst clinicians and scientists from different disciplines, which will be the trend in the coming decades.
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