AUTHOR=Meng Jiahong , Zhou Chenhe , Hu Bin , Luo Mengmeng , Yang Yute , Wang Yangxin , Wang Wei , Jiang Guangyao , Hong Jianqiao , Li Sihao , Wu Haobo , Yan Shigui , Yan Weiqi TITLE=Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation JOURNAL=Frontiers in Pharmacology VOLUME=9 YEAR=2018 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.01053 DOI=10.3389/fphar.2018.01053 ISSN=1663-9812 ABSTRACT=

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.