title: (-)-Epigallocatechin-3-gallate suppresses osteoclast differentiation and ameliorates experimental arthritis in mice.
abstract: OBJECTIVE
  To verify the effects of (-)-epigallocatechin-3-gallate (EGCG) on osteoclast differentiation and on experimental arthritis in mice.
  
  
  METHODS
  Human osteoclasts were differentiated from peripheral blood monocytes. The effects of EGCG were examined by tartrate-resistant acid phosphatase (TRAP) staining, bone resorption assay, Western blotting, and quantitative real-time polymerase chain reaction. Arthritis was induced in mice by injecting a cocktail of monoclonal antibodies against collagen. EGCG (20 microg/gm body weight) was administered intraperitoneally every day from day 0 through the end of the experiments (day 15). The effects of EGCG were determined by assessments of joint swelling, histologic changes, and TRAP staining on day 15.
  
  
  RESULTS
  EGCG reduced the generation of TRAP-positive multinucleated cells, bone resorption activity, and osteoclast-specific gene expression without affecting cell viability. EGCG down-regulated expression of nuclear factor of activated T cells c1 (NF-ATc1), but not of NF-kappaB, c-Fos, and c-Jun, suggesting that down-regulation of NF-ATc1 is one of the molecular bases of EGCG action. Additionally, EGCG treatment ameliorated clinical symptoms and reduced histologic scores in arthritic mice (P < 0.05). The in vivo effect of EGCG on osteoclast differentiation was not clear in this model, probably because EGCG suppressed the inflammation itself.
  
  
  CONCLUSIONS
  EGCG suppressed osteoclast differentiation and ameliorated experimental arthritis in mice over the short term. It remains to be established whether EGCG is useful for the prevention and treatment of osteoporosis and rheumatoid arthritis.
authors.affiliation: Evidence-Based Laboratory Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. morinobu@med.kobe-u.ac.jp
authors.forename: Akio
authors.initials: A
authors.lastname: Morinobu
authors.forename: Wang
authors.initials: W
authors.lastname: Biao
authors.forename: Shino
authors.initials: S
authors.lastname: Tanaka
authors.forename: Marika
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Liu
authors.initials: L
authors.lastname: Jun
authors.forename: Goh
authors.initials: G
authors.lastname: Tsuji
authors.forename: Yoshitada
authors.initials: Y
authors.lastname: Sakai
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kurosaka
authors.forename: Shunichi
authors.initials: S
authors.lastname: Kumagai
mesh_terms: D000818:Animals; D016587:Antimutagenic Agents / Q000494:pharmacology*; D001168:Arthritis / Q000188:drug therapy*; D015153:Blotting, Western; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D004195:Disease Models, Animal; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D016587:Antimutagenic Agents; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D002392:Catechin; C045651:epigallocatechin gallate