Chlorpyrifos promotes chondrocyte pyroptosis to induce articular cartilage degeneration via activating NF-κB signaling

Chlorpyrifos (CPF), a widely used pesticide, poses significant risks to human and animal health through environmental and food exposure. While its detrimental effects on the nervous, cardiovascular, and endocrine systems are well-documented, its impact on knee joint health remains poorly understood. In this study, 4-week-old male C57BL/6 mice were exposed to CPF via intragastric administration at doses of 3 and 6 mg/kg for durations of 4 and 8 weeks. Osteoarthritis (OA) severity and associated molecular alterations in knee joints were evaluated by hematoxylin and eosin (H&E) staining, Safranin O/Fast Green staining, immunohistochemistry, and immunofluorescence. Our results showed that CPF exposure led to knee joint injury, characterized by articular cartilage degeneration and subchondral bone loss. Notably, CPF induced both apoptosis and pyroptosis of chondrocytes via activation of the NF-κB signaling pathway, with pyroptosis appearing to be the predominant mechanism at lower doses and shorter exposure durations. Collectively, our findings provide novel insights into CPF's role in exacerbating articular cartilage degeneration by activating chondrocyte pyroptosis, underscoring its contribution to knee joint damage and OA-like progression.