Exp Mol Med.
2011 Jul;43(7):411-418. 10.3858/emm.2011.43.7.045.
Inhibitory effect of (-)-epigallocatechin gallate on titanium particle-induced TNF-alpha release and in vivo osteolysis
- Affiliations
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- 1Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Kyungpook National University, Daegu 700-412, Korea. epark@knu.ac.kr, syukim@knu.ac.kr
- 2Department of Pathology and Regenerative Medicine, School of Dentistry, Kyungpook National University, Daegu 700-412, Korea.
- 3Department of Orthopaedic Surgery, School of Medicine, Kyungpook National University, Daegu 700-412, Korea.
- KMID: 1015460
- DOI: http://doi.org/10.3858/emm.2011.43.7.045
Abstract
- 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.
Keyword
MeSH Terms
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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
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