Cigarette and Electronic Cigarette Exposure in Osteoarthritis: Immune Dysregulation and Inflammatory Signaling Pathways

Osteoarthritis (OA) was once seen mainly as a degenerative joint disease, but more studies now show that inflammation also has an important role in its development and progression. Smoking may be one factor in this process. Findings from population studies are still not fully consistent, but cigarette exposure is known to affect immune function and inflammatory signaling. This suggests that its role in OA may be more complex than a simple risk factor. At the same time, the fast growth of electronic cigarettes (EC) use has raised new concerns, because its effects on joint tissues are still not clear. In this Perspective, we discuss how cigarette and EC exposure may affect OA through several related pathways, including synovial macrophage activation, damage-associated molecular pattern (DAMP)-mediated signaling, NF-κB activation, inflammasome activation, Th17/Treg imbalance, and changes in microRNA expression. These changes may disturb the synovial-cartilage microenvironment, increase cytokine and chemokine production, and promote joint tissue damage. We also discuss current problems in this field, such as inconsistent epidemiological results, limited OA-specific mechanistic studies, and the lack of reliable models for EC exposure.