Environmental high temperature (heat stroke) causes articular cartilage damage in vivo and in vitro.

Abstract

Heatstroke (HS) is gradually becoming a major challenge in the field of global public health with the trend of global warming. In recent years, extreme high-temperature weather events have occurred frequently in the world, which directly led to a significant increase in heatstroke. However, up to now, the potential pathological effects of HS on articular cartilage have not been revealed. Therefore, in our current work, we studied the damage of heat toxicity on chondrocytes in vitro. The results showed that heatstroke reduced the cell activity of chondrocytes and triggered a decrease in mitochondrial membrane potential and oxidative stress response. Further biochemical analysis showed that heatstroke caused chondrocyte PANoptosis. On this basis, we further analyzed the molecular mechanism of HS-induced cartilage damage. The results showed that HS activated ZBP-1-mediated PAN-apoptosis. In vivo, our group further evaluated the impact of HS on articular cartilage. The results showed that heatstroke caused damage to articular cartilage, and immunohistochemistry showed that heatstroke caused damage and programmed necrosis of cartilage tissue. On this basis, we evaluated the alleviating effect of FGF21 on HS-induced chondrocyte damage. The results showed that FGF21 could effectively alleviate the PANoptosis of chondrocytes caused by heatstroke via activating the AMPK signaling (at least partially). In summary, the current research lays a foundation for further exploring the cartilage damage caused by heatstroke.