4-Octyl itaconate inhibits synovitis in the mouse model of post-traumatic osteoarthritis and alleviates pain  

作　　者：Yu-Zhen Tang Wan Chen Bao-Yun Xu Gang He Xiu-Cheng Fan Kang-Lai Tang 

机构地区：[1]Department of Orthopaedics/Sport Medicine Center,First Affiliated Hospital of Army Medical University,Chongqing,400000,China [2]Department of Training Injury Prevention,Army Medical University,Chongqing,400000,China

出　　处：《Chinese Journal of Traumatology》2025年第1期50-61,共12页中华创伤杂志(英文版)

基　　金：supported by the Foundation of Chongqing Talents(grant no.CQYC2021059825).

摘　　要：Purpose:To investigate the pathological changes of the synovium in mice with post-traumatic osteoarthritis(PTOA)treated with 4-octyl itaconate(4-OI)and evaluate the therapeutic effects of 4-OI.Methods:In the phenotypic validation experiment,the mice were randomly divided into 3 groups:wildtype(WT)group,sham group,and destabilization of the medial meniscus(DMM)group.Through MRI,micro-CT,and histological analysis,it was determined that the DMM surgery induced a mouse PTOA model with significant signs of synovitis.At 12 weeks post-DMM surgery,synovial tissues from the DMM group and WT group mice were collected for ribonucleic acid sequencing analysis.In the 4-OI treatment experiment,mice were randomly divided into the sham group,DMM group,DMM+4-OI(50 mg/kg)group,and DMM+4-OI(100 mg/kg)group.Von Frey tests and open field tests were conducted at intervals during the 12 weeks following the DMM surgery.After 12 weeks of surgery,the efficacy of 4-OI treatment on PTOA in mice was evaluated using MRI,micro-CT,histological analysis,and quantitative real-time polymerase chain reaction.Finally,we utilized network pharmacology analysis to predict the mechanism of 4-OI in treating PTOA synovitis and conducted preliminary validation.Statistical analysis was performed using one-way ANOVA and the Kruskal-Wallis test.Difference was considered statistically significant at p<0.05.Results:The DMM surgery effectively induced a PTOA mouse model,which displayed significant symptoms of synovitis.These symptoms included a notable increase in both the number of calcified tissues and osteophytes(p<0.001),an enlargement of the calcified meniscus and synovial tissue volume(p<0.001),and thickening of the synovial lining layer attributable to M1 macrophage accumulation(p=0.035).Additionally,we observed elevated histological scores for synovitis(p<0.001).Treatment with 4-OI inhibited the thickening of M1 macrophages in the synovial lining layer of PTOA mice(p<0.001)and reduced fibrosis in the synovial stroma(p=0.004).Furthermore,it reduced the hi

关 键 词：4-Octyl itaconate SYNOVITIS Post-traumaticosteoarthritis PAIN 

分 类 号：R686.7[医药卫生—骨科学]