Objective

Osteoarthritis (OA) is a chronic arthropathy that frequently occurs in the middle-aged and elderly population. The aim of this study was to investigate the molecular mechanism of OA based on autophagy theory.

Design

We downloaded the gene expression profile from the Gene Expression Omnibus repository. Differentially expressed genes (DEGs) related to the keyword “autophagy” were identified using the scanGEO online analysis tool. DEGs representing the same expression trend were screened using the MATCH function. Clinical synovial specimens were collected for identification, pathological diagnosis, hematoxylin and eosin staining, and real-time polymerase chain reaction analysis. Differential expression of mRNAs in the synovial membrane tissues and chondrocyte monolayer samples from OA patients was used to identify potential OA biomarkers. Protein-protein interactions were established by the STRING website and visualized with Cytoscape. Functional and pathway enrichment analyses were performed using the Metascape database.

Results

GABARAPL1, GABARAPL2, and ATG13 were obtained as co-expressed autogenes in the 3 data sets. They were all downregulated among OA synovial tissues compared with non-OA synovial tissues (P < 0.01). A protein-protein interaction network was constructed based on these 3 genes and included 63 genes. A functional analysis revealed that these genes were associated with autophagy-related functions. The top hub genes in the protein-protein interaction network were presented. Furthermore, 3 key modules were extracted to be core control modules.

Conclusions

These results offer an important molecular understanding of the key transcriptional regulatory genes and modules based on the network of potential autophagy mechanisms in human OA.

中文翻译：

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基于自噬网络的转录调控识别人类骨关节炎的关键基因和潜在机制。

客观的

骨关节炎（Osteoarthritis，OA）是一种常见于中老年人群的慢性关节病。本研究的目的是基于自噬理论研究 OA 的分子机制。

设计

我们从 Gene Expression Omnibus 存储库下载了基因表达谱。使用 scanGEO 在线分析工具鉴定与关键词“自噬”相关的差异表达基因 (DEG)。使用 MATCH 函数筛选代表相同表达趋势的 DEG。采集临床滑膜标本进行鉴定、病理诊断、苏木精伊红染色、实时聚合酶链反应分析。来自 OA 患者的滑膜组织和软骨细胞单层样本中 mRNA 的差异表达被用来识别潜在的 OA 生物标志物。蛋白质-蛋白质相互作用由 STRING 网站建立并用 Cytoscape 可视化。使用 Metascape 数据库进行功能和通路富集分析。

结果

GABARAPL1、GABARAPL2 和 ATG13 在 3 个数据集中作为共表达的自体基因获得。与非 OA 滑膜组织相比，它们在 OA 滑膜组织中均下调（P < 0.01）。基于这3个基因构建了一个蛋白质-蛋白质相互作用网络，包括63个基因。功能分析显示这些基因与自噬相关功能有关。介绍了蛋白质-蛋白质相互作用网络中的顶级枢纽基因。此外，还提取了3个关键模块作为核心控制模块。

结论

这些结果为基于人类 OA 中潜在自噬机制网络的关键转录调控基因和模块提供了重要的分子理解。