Inhibitory effect of (-)-epigallocatechin gallate on titanium particle-induced TNF-α release andin vivoosteolysis

Shan Jin,Eui Kyun Park,Ju-Young Park,Hong-In Shin,Shin-Yoon Kim,Jung-Min Hong,Tae-Ho Kim

doi:10.3858/emm.2011.43.7.045

Shan Jin, Eui Kyun Park + Show 5 more

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https://doi.org/10.3858/emm.2011.43.7.045

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Abstract

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-a 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.

Highlights

Periprosthetic osteolysis and subsequent aseptic loosening by wear debris of orthopaedic implants are the most common causes of total joint arthroplasty (TJA) failure
The particle-induced release of Tumor necrosis factor-α (TNF-α) and IL-6 in macrophages depends on tyrosine and serine/threonine kinase activity leading to the activation of nuclear factor-κB (NF-κB) and NF-interleukin-6 (NF-IL-6), which are critical for the upregulation of proinflammatory cytokines (Nakashima et al, 1999)
The results demonstrate that epigallocatechin gallate (EGCG) has a dose-dependent inhibitory effect on Ti particle-induced TNF-α release in macrophages

Summary

Introduction

Periprosthetic osteolysis and subsequent aseptic loosening by wear debris of orthopaedic implants are the most common causes of total joint arthroplasty (TJA) failure. The debris induces the production of inflammatory cytokines and peptide factors such as TNF-α, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-11, macrophage chemoattractant protein-1, and granulocytemonocyte colony-stimulating factor, which are involved in osteolysis and bone loosening (Kim et al, 1993; Sabokbar and Rushton 1995; Al-Saffar et al, 1996; Xu et al, 1998; Merkel et al, 1999; Kaufman et al, 2008). Controlling the synthesis of TNF-α and other inflammatory cytokines in the periprosthetic environment may be a potential target to prevent or reduce wear particle-induced osteolysis (Schwarz et al, 2000)

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