Inhibitory effect of (-)-epigallocatechin gallate on titanium particle-induced TNF-α release and in vivo osteolysis

Tumor necrosis factor-α (TNF-α) and inflammatory cytokines released from activated macrophages in response to particulate debris greatly impact periprosthetic bone loss and consequent implant failure. In the present study, we found that a major polyphenolic component of green tea, (-)-epigallocatechin gallate (EGCG), inhibited Ti particle-induced TNF- α release in macrophages in vitro and calvarial osteolysis in vivo. The Ti stimulation of macrophages released TNF-α in a dose- and time-dependent manner, and EGCG substantially suppressed Ti particle-induced TNF-α release. Analysis of signaling pathway showed that EGCG inhibited the Ti-induced c-Jun N-terminus kinase (JNK) activation and inhibitory κB (IκB) degradation, and consequently the Ti-induced transcriptional activation of AP-1 and NF-κB. In a mouse calvarial osteolysis model, EGCG inhibited Ti particle-induced osteolysis in vivo by suppressing TNF-α expression and osteoclast formation. Therefore, EGCG may be a potential candidate compound for osteolysis prevention and treatment as well as aseptic loosening after total replacement arthroplasty.