Identification of Potential Common Pathogenic Mechanisms Underlying Osteoarthritis and Major Depressive Disorder...

Patients with osteoarthritis (OA) exhibit an elevated risk for major depressive disorder (MDD), primarily due to chronic pain and associated disability. However, the shared molecular mechanisms underlying these conditions remain poorly understood.

This study employs bioinformatics and systems biology approaches to identify common gene signatures and elucidate the shared pathogenesis of OA and MDD.

We identified 22 common differentially expressed genes between the two diseases, which were predominantly associated with the positive regulation of reactive oxygen species metabolic processes, immune and inflammatory responses, efferocytosis, the PI3K-Akt signaling pathway, the TGF-beta receptor signaling pathway, and immune system-related pathways. Notably, CXCR6, GZMK, and KLRG1 were identified as key genes, showing positive correlations with CD8+ T cells and negative correlations with naïve CD4+ T cells and monocytes in both OA and MDD. Competitive endogenous RNA regulatory network analysis revealed that the KCNQ1OT1-miR-92a/miR-132/miR-19b/miR-145-CXCR6/GZMK/KLRG1 and XIST1-miR-92a/miR-132/miR-19b-CXCR6/GZMK/KLRG1 regulatory axes may play critical roles in the pathogenesis of OA and MDD.

These findings provide novel insights into the comorbidity mechanism of OA and MDD and may guide the development of individualized therapeutic strategies for patients with comorbid conditions.