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在一项骨关节炎滑液外泌体研究中鉴定外泌体 mRNA、lncRNA 和 circRNA 特征。

Identification of exosomal mRNA, lncRNA and circRNA signatures in an osteoarthritis synovial fluid-exosomal study.

机构信息

Department of Orthopaedics, The Second Affiliated Hospital of Shenzhen University, The Second School of Clinical Medicine, Southern Medical University, The Clinical Medical College of Guangdong Medical University, People's Hospital of Shenzhen Baoan District, China.

The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.

出版信息

Exp Cell Res. 2022 Jan 1;410(1):112881. doi: 10.1016/j.yexcr.2021.112881. Epub 2021 Nov 12.

Abstract

AIMS

Osteoarthritis (OA) is a common degenerative disease that is pathologically characterized by destruction of the joint matrix and reduction of articular chondrocytes, resulting in joint deformity and motor dysfunction. However, the molecular mechanisms governing this pathology have not been elucidated to date.

METHODS

In this study, we determined the expression levels of lncRNAs, circRNAs, and mRNAs extracted from synovial exosomes of OA and control patients. A network of circRNA/lncRNA-miRNA-mRNA interactions was established using MiRanda and TargetScan software to explore OA pathogenesis. The exosomal lncRNA, circRNA and mRNA expression profiles of the OA and control groups were analysed using LC human competing endogenous RNA (ceRNA) microarrays. The differentially expressed genes were analysed to determine their potential roles in the pathogenesis of OA by bioinformatic analysis.

RESULTS

There were 52 mRNAs, 196 lncRNAs and 98 circRNAs differentially expressed in synovial exosomes between osteoarthritis synovial and the control group. The final ceRNA network of lncRNAs and circRNAs exhibited a complex interaction between ncRNA and mRNA related to OA pathological mechanisms. An intersection analysis of the ceRNA network showed that 22 miRNAs, 45 lncRNAs, and 34 circRNAs enriched in the PI3K/Akt and autophagy pathways correlated with 7 mRNAs and may play important roles in OA pathological mechanisms.

CONCLUSION

Our work analysed mRNA/lncRNA/circRNA expression and displayed the ceRNA network of lncRNAs and circRNAs to profile the pathogenesis of OA in synovial exosomes. The results of this study may help to elucidate the pathogenesis of OA and may provide important references for further research attempting to identify more effective targets for the diagnosis and therapy of OA.

摘要

目的

骨关节炎(OA)是一种常见的退行性疾病,其病理特征为关节基质破坏和关节软骨细胞减少,导致关节畸形和运动功能障碍。然而,迄今为止,尚不清楚控制这种病理学的分子机制。

方法

在这项研究中,我们确定了从 OA 和对照组患者的滑膜外泌体中提取的 lncRNA、circRNA 和 mRNA 的表达水平。使用 MiRanda 和 TargetScan 软件建立了 circRNA/lncRNA-miRNA-mRNA 相互作用网络,以探讨 OA 的发病机制。使用 LC 人类竞争性内源性 RNA(ceRNA)微阵列分析 OA 和对照组滑膜外泌体的 lncRNA、circRNA 和 mRNA 表达谱。通过生物信息学分析,对差异表达基因进行分析,以确定它们在 OA 发病机制中的潜在作用。

结果

在 OA 滑膜与对照组之间的滑膜外泌体中,有 52 个 mRNAs、196 个 lncRNAs 和 98 个 circRNAs 表达差异。最终的 lncRNA 和 circRNA 的 ceRNA 网络显示了 ncRNA 和与 OA 病理机制相关的 mRNA 之间复杂的相互作用。ceRNA 网络的交集分析表明,PI3K/Akt 和自噬途径中富集的 22 个 miRNA、45 个 lncRNA 和 34 个 circRNA 与 7 个 mRNA 相关,可能在 OA 病理机制中发挥重要作用。

结论

我们的工作分析了 mRNA/lncRNA/circRNA 的表达,并显示了 lncRNA 和 circRNA 的 ceRNA 网络,以描绘滑膜外泌体中 OA 的发病机制。本研究的结果可能有助于阐明 OA 的发病机制,并为进一步研究寻找更有效的 OA 诊断和治疗靶点提供重要参考。

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