Figure 5. Transcriptional Profiling of Mitochondrial Treatment in Human Osteoarthritis Chondrocytes reveal cytokine-mediated immune response.

(A) Volcano plot illustrating differential gene expression, with log fold change plotted against -log10 adjusted p-values. Genes surpassing significance thresholds are highlighted, demonstrating substantial dowregulation (e.g., FOS, EGR1) and upregulation (e.g., RSAD2, IFIT1/2, IFIH1, TSPYL6), indicative of mitochondrial treatment-induced transcriptional changes.

(B) Heatmap depicting RMA intensity of significant genes (False Discovery Rate < 0.05). Gene names are annotated on the y-axis. Expression levels are represented by a color gradient, with blue indicating lower expression and red indicating higher expression across samples.

(C) Bar plots for pathway enrichment analyses. The left bar plot represents Gene Ontology (GO) Biological Process enrichment, revealing significant terms such as "response to stress", "defense response" and "immune system process," which highlight an activation of immune and stress-related pathways. The low-right bar plot displays Reactome Pathway enrichment, with significant involvement in "Interferon Signaling" and "Cytokine Signaling in Immune system," emphasizing a robust immune response. Adjacent to the pathway enrichment, transcription factor (TF) analysis bar plot shows transcription factors with significant regulatory potential involved in interferon/adaptative immune response.

(D) Protein-protein interaction network from STRING analysis, where nodes represent proteins and edges indicate known and predicted interactions. Key proteins acting as interaction hubs are accentuated, suggesting their central role in the cellular response to mitochondrial treatment. Strong network was found among induced immune genes after mitochondrial treatment.