Regulation of cartilage damage caused by lack of Klotho with thioredoxin/peroxiredoxin (Trx/Prx) system and succedent NLRP3 activation in osteoarthritis mice.

This present study aims to verify the underlying mechanism that anti-aging protein Klotho protects cartilages against the damage induced by oxidative stress. The Klotho expression level in the articular cartilages of mice with osteoarthritis (OA) was measured by using western blotting and quantitative real-time PCR. This work also investigated the effects of Klotho on chondrocyte functions, such as PI3K/Akt pathway, apoptosis and reactive oxygen species (ROS) production, through overexpressing Klotho in chondrocytes by transfecting with the plasmid encoding Klotho. The results showed that Klotho expression level obviously decreased in the articular cartilages of OA mice. It was also found that mechanical loading significantly reduced the expression and activity of Klotho in chondrocytes. In addition, the overexpression of Klotho suppressed chondrocyte apoptosis through thioredoxin/peroxiredoxin (Trx/Prx) family and ROS/TXNIP/NLRP3 signaling pathways. All these above findings suggest that Klotho is essential in OA progression, and may be a good target for the research and development of the drugs for OA treatment.