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 oxi...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 NRF_(2)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/NRF_(2)signaling pathway,which underscores the potential of CeO_(2)NPs for application in the treatment of enthesopathy healing.展开更多
基金the National Natural Science Foundation of China(Nos.81941009,81991514,32271409,and 82202778)Nanjing Distinguished Youth Fund(No.JQX20001)+3 种基金Jiangsu Provincial Key R&D Program(No.BE2022836)China Postdoctoral Science Foundation(No.2020M671456)National Basic Research Program of China(No.2021YFA1201404)Jiangsu Provincial Key Medical Center Foundation,Jiangsu Provincial Medical Outstanding Talent Foundation,Jiangsu Provincial Medical Youth Talent Foundation and Jiangsu Provincial Key Medical Talent Foundation,and the Fundamental Research Funds for the Central Universities(Nos.14380493 and 14380494).
文摘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 NRF_(2)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/NRF_(2)signaling pathway,which underscores the potential of CeO_(2)NPs for application in the treatment of enthesopathy healing.
