Dihydroartemisinin ameliorates hemarthrosis-induced cartilage degeneration by suppressing chondrocyte senescence via activation of Keap1-Nrf2 signaling pathway.

Background: Joint bleeding (hemarthrosis) is a major manifestation of joint trauma, especially repeated and spontaneous in hemophilia patients. Hemarthrosis has been identified to induce the excessive reactive oxygen species (ROS) accumulation and permanent damage in articular cartilage. Dihydroartemisinin (DHA), a well-known clinical anti-malaria drug with few sides effects therapy, has been reported to possess anti-oxidative activity. This study was aimed at exploring the effect of DHA on blood-induced cartilage erosion and its underlying mechanisms. Methods: Two distinct hemarthrosis models were constructed respectively by fresh blood joint injection in WT and joint needle puncture in Results: DHA remarkably ameliorated the cartilage degeneration in both two hemarthrosis models. Similarly, Conclusion: Our findings indicate that DHA effectively reduces chondrocyte senescence and mitigates cartilage destruction following hemarthrosis via activation of Nrf2/Keap1 signaling pathway. The Translational potential of this article: On the one hand, this study highlights the important role of chondrocyte senescence in hemarthrosis-induced cartilage degradation, implying that inhibiting chondrocyte senescence may be a viable therapeutic strategy for blood-induced arthropathy. On the other hand, our findings demonstrate the remarkable chondroprotective effect of DHA in bleeding joint by modulating the Nrf2/Keap1 anti-oxidative signaling pathway, suggesting DHA may serve as a potential candidate drug for the therapy of blood-induced arthropathy.