Tumor necrosis factor-alpha (TNF-alpha) 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-alpha release in macrophages in vitro and calvarial osteolysis in vivo. The Ti stimulation of macrophages released TNF-alpha in a dose- and time-dependent manner, and EGCG substantially suppressed Ti particle-induced TNF-alpha release. Analysis of signaling pathway showed that EGCG inhibited the Ti-induced c-Jun N-terminus kinase (JNK) activation and inhibitory kappaB (IkappaB) degradation, and consequently the Ti-induced transcriptional activation of AP-1 and NF-kappaB. In a mouse calvarial osteolysis model, EGCG inhibited Ti particle-induced osteolysis in vivo by suppressing TNF-alpha 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.
Animals ; Catechin/*analogs & derivatives/pharmacology ; Cell Line ; Implants, Experimental ; Macrophages/drug effects/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinase 8/metabolism ; NF-kappa B/metabolism ; Osteolysis/chemically induced/*metabolism/prevention & control ; Particulate Matter/*adverse effects ; Prosthesis Failure ; Signal Transduction/drug effects ; Skull/*drug effects/pathology ; Titanium/*adverse effects ; Transcription Factor AP-1/metabolism ; Tumor Necrosis Factor-alpha/*metabolism