Department of Orthopedics, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200062, China.
Orthopaedic Center, Zhengzhou 460 Hospital, Zhengzhou, 450007, China.
J Orthop Surg Res. 2024 Nov 5;19(1):722. doi: 10.1186/s13018-024-05207-8.
This study seeks to elucidate the expressions of lncRNA TSIX in Osteoarthritis (OA) and to explore its mechanisms in regulating OA progression.
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.
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.
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.
本研究旨在阐明长链非编码 RNA TSIX 在骨关节炎（OA）中的表达，并探讨其调节 OA 进展的机制。
采用 RT-qPCR 分析 OA 患者按 Kellgren-Lawrence（K-L）分级的 TSIX 表达。采用受试者工作特征（ROC）曲线评估 TSIX 的诊断价值。采用 Pearson 方法评估 TSIX 水平与 Lysholm 和视觉模拟评分（VAS）评分等临床评分之间的相关性。采用白细胞介素-1β（IL-1β）诱导的 SW1353 细胞作为体外模型。通过流式细胞术和细胞计数试剂盒-8（CCK-8）检测评估细胞功能。通过荧光素酶报告系统验证 TSIX 与 miR-320a 之间的关系，同时利用生物信息学方法预测 miR-320a 的下游靶基因。
结果表明，OA 患者的 TSIX 水平高于对照组，随着 K-L 分级的升高，TSIX 表达呈显著递增趋势。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 通过靶向 miR-320a 增强细胞活力并减轻 IL-1β诱导的细胞凋亡，同时促进 Aggrecan 和 Collagen II 的分泌。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 OA 患者中 TSIX 的表达增加。提示 TSIX 可能通过调节 miR-320a/PTEN 轴在 OA 中软骨细胞功能障碍中发挥作用。
