%0 Figure %A Meng, Jiahong %A Zhou, Chenhe %A Hu, Bin %A Luo, Mengmeng %A Yang, Yute %A Wang, Yangxin %A Wang, Wei %A Jiang, Guangyao %A Hong, Jianqiao %A Li, Sihao %A Wu, Haobo %A Yan, Shigui %A Yan, Weiqi %D 2018 %T Image_1_Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation.TIF %U https://frontiersin.figshare.com/articles/figure/Image_1_Stevioside_Prevents_Wear_Particle-Induced_Osteolysis_by_Inhibiting_Osteoclastogenesis_and_Inflammatory_Response_via_the_Suppression_of_TAK1_Activation_TIF/7133642 %R 10.3389/fphar.2018.01053.s001 %2 https://frontiersin.figshare.com/ndownloader/files/13125116 %K aseptic loosening %K osteoclast %K NF-κB – nuclear factor-kappa B %K MAPK %K TAK1 %X

Aseptic loosening and periprosthetic osteolysis are the leading causes of total joint arthroplasty failure, which occurs as a result of chronic inflammatory response and enhanced osteoclast activity. Here we showed that stevioside, a natural compound isolated from Stevia rebaudiana, exhibited preventative effects on titanium particle-induced osteolysis in a mouse calvarial model. Further histological assessment and real-time PCR analysis indicated that stevioside prevented titanium particle-induced osteolysis by inhibiting osteoclast formation and inflammatory cytokine expression in vivo. In vitro, we found that stevioside could suppress RANKL-induced osteoclastogenesis and titanium particle-induced inflammatory response in a dose-dependent manner. Mechanistically, stevioside achieved these effects by disrupting the phosphorylation of TAK1 and subsequent activation of NF-κB/MAPKs signaling pathways. Collectively, our data suggest that stevioside effectively suppresses osteoclastogenesis and inflammatory response both in vitro and in vivo, and it might be a potential therapy for particle-induced osteolysis and other osteolytic diseases.

%I Frontiers