Cerium Oxide Nanozymes Alleviate Oxidative Stress in Tenocytes for Achilles Tendinopathy Healing

Background Reactive oxygen species (ROS) is considered as ubiquitous and highly active chemicals that influence tendon integrity and orchestrate tendon repair. With significant recent advances in nanomaterials, cerium oxide nanoparticles (CeO 2 NPs) exhibit superoxide dismutase- and catalase-like activities. Herein, we introduced a therapeutic approach of CeO 2 NPs for Achilles tendinopathy (AT) healing. Methods CeO 2 NPs were synthesized to examine their effect as ROS scavengers on AT healing in vitro and in vivo. The mRNA levels of inflammatory factors were evaluated in AT after CeO 2 NPs treatment in vitro. The mechanisms underlying CeO 2 NPs-mediated stimulation of NRF2 translocation and ERK signaling were verified through immunofluorescence and Western blot analysis. The efficacy of CeO 2 NPs was tested in an AT rat model in comparison with the control. Results CeO 2 NPs not only significantly scavenged multiple ROS and suppressed ROS-induced inflammatory reactions but also protected cell proliferation under oxidative stress induced by tert-butyl hydroperoxide (TBHP). Moreover, CeO 2 NPs could promote NRF2 nuclear translocation for anti-oxidation and anti-inflammation through the ERK signaling pathway. In a rat model of collagenase-induced tendon injuries, CeO 2 NPs showed significant therapeutic efficacy by ameliorating tendon damage. Conclusion The present study provides valuable insights into the molecular mechanism of CeO 2 NPs to ameliorate ROS in tenocytes via the ERK/NRF2 signaling pathway, which underscores the potential of CeO 2 NPs for application in the treatment of enthesopathy healing.