10.3389/fphar.2018.01053.s001 Jiahong Meng Jiahong Meng Chenhe Zhou Chenhe Zhou Bin Hu Bin Hu Mengmeng Luo Mengmeng Luo Yute Yang Yute Yang Yangxin Wang Yangxin Wang Wei Wang Wei Wang Guangyao Jiang Guangyao Jiang Jianqiao Hong Jianqiao Hong Sihao Li Sihao Li Haobo Wu Haobo Wu Shigui Yan Shigui Yan Weiqi Yan Weiqi Yan Image_1_Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation.TIF Frontiers 2018 aseptic loosening osteoclast NF-κB – nuclear factor-kappa B MAPK TAK1 2018-09-26 13:30:21 Figure 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 <p>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.</p>