title: Inhibitory effect of (-)-epigallocatechin gallate on titanium particle-induced TNF-α release and in vivo osteolysis.
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.
authors.affiliation: Skeletal Diseases Genome Research Center Kyungpook National University Hospital.
authors.forename: Shan
authors.initials: S
authors.lastname: Jin
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Park
authors.forename: Jung Min
authors.initials: JM
authors.lastname: Hong
authors.forename: Tae Ho
authors.initials: TH
authors.lastname: Kim
authors.forename: Hong In
authors.initials: HI
authors.lastname: Shin
authors.forename: Eui Kyun
authors.initials: EK
authors.lastname: Park
authors.forename: Shin Yoon
authors.initials: SY
authors.lastname: Kim
mesh_terms: D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D020007:Implants, Experimental; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D052638:Particulate Matter / Q000009:adverse effects*; D011475:Prosthesis Failure; D015398:Signal Transduction / Q000187:drug effects; D012886:Skull / Q000187:drug effects* / Q000473:pathology; D014025:Titanium / Q000009:adverse effects*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D052638:Particulate Matter; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D002392:Catechin; C045651:epigallocatechin gallate; D014025:Titanium; D048055:Mitogen-Activated Protein Kinase 8