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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.

Stevioside Prevents Wear Particle-Induced Osteolysis by Inhibiting Osteoclastogenesis and Inflammatory Response via the Suppression of TAK1 Activation