Mitochondria-Related Gene MAOB is a Key Biomarker of Osteoarthritis and Inhibition of Its Expression Reduces LPS-induced Chondrocyte Damage.

Abstract

The mitochondria are an important organelle in cells responsible for producing energy, and its abnormal function is closely related to the occurrence and development of osteoarthritis. Finding key genes associated with mitochondrial dysfunction in osteoarthritis can provide new ideas for the study of its pathogenesis. Firstly, 371 differential expressed genes (DEGs) were obtained through bioinformatics analysis of the GSE12021 and GSE55235 datasets in the GEO database, and 24 mitochondria-related DEGs (Mito-DEGs) were obtained by crossing differential genes with mitochondrial related genes. Next, KEGG and GO analysis of Mito-DEGs showed that upregulated Mito-DEGs were mainly enriched in small molecule catabolic process and tryptophan metabolism, while downregulated Mito-DEGs were mainly enriched in acetyl-CoA metabolic process and fatty acid biosynthesis. Furthermore, the key genes ME2 and MAOB were obtained through protein-protein interaction network analysis and lasso cox analysis of the 24 Mito-DEGs. In addition, the comparison results of immune cell scores showed differences between T cells CD4 memory resting, T cells regulatory (Tregs), Mast cells resting, and Mast cells activated in the OA group and the control group. More importantly, the potential regulatory mechanisms of key genes were studied through GSEA analysis and their correlation with immune infiltrating cells, immune checkpoints, m6A, and ferroptosis. Finally, in LPS-induced C28/I2 cells, silencing MAOB reduced inflammation injury and inhibited mitochondrial damage. Our research findings suggest that MAOB may hold potential as a target for the diagnosis and treatment of osteoarthritis.