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KMID : 0620920110430070411
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Experimental & Molecular Medicine
2011 Volume.43 No. 7 p.411 ~ p.418
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Inhibitory effect of (-)-epigallocatechin gallate on titanium particle-induced TNF-α release and in vivo osteolysis
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Jin Shan
Park Ju-Young
Hong Jung-Min
Kim Tae-Ho
Shin Hong-In
Park Eui-Kyun
Kim Shin-Yoon
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Abstract
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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.
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KEYWORD
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epigallocatechin gallate, mitogen-activated protein kinases, transcription factor AP-1, NF-κB, titanium, tumor necrosis factor-α
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