Transcriptional Regulation Based on Network of Autophagy Identifies Key Genes and Potential Mechanisms in Human Osteoarthritis

Abstract

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.