title: Inhibition mechanism of Qingluo Tongbi Granule () on osteoclast differentiation induced by synovial fibroblast and monocytes co-culture in adjuvant-induced arthritic rats.
abstract: OBJECTIVE
  To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (, QTG) on osteoclast differentiation in rheumatoid arthritis in rats.
  
  
  METHODS
  Fibroblast and monocyte co-culture were used to induce osteoclast differentiation in adjuvant-induced arthritic (AIA) rats. Serum containing QTG was prepared and added to the osteoclasts, and activation of the tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase/nuclear factor of activated T cells, cytoplasmic1 (TRAF6/MAPK/NFATc1) pathways was examined.
  
  
  RESULTS
  The induced osteoclasts were multinucleated and stained positive for tartrate-resistant acid phosphatase (TRAP) staining. Serum containing QTG at 14.4, 7.2 or 3.6 g/kg inhibited the activation of TRAF6, extracellular regulated protein kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 and decreased the percentage of cells with nuclear NFATc1 in a dose-dependent manner, the high and middle doses exhibited clear inhibitory activity (P<0.01 and P<0.05, respectively). After the addition of MAPK inhibitors, the NFATc1 expression showed no significant difference compared with the control group (P>0.05).
  
  
  CONCLUSIONS
  Serum containing QTG could generally inhibit the TRAF6/MAPK pathways and possibly inhibit the NFATc1 pathway. In addition, QTG may regulate other signaling pathways that are related to osteoclast differentiation and maturation.
authors.affiliation: Nanjing University of Chinese Medicine, Nanjing, 210023, China.
authors.forename: Tian-yang
authors.initials: TY
authors.lastname: Liu
authors.forename: Ling-ling
authors.initials: LL
authors.lastname: Zhou
authors.forename: Cong
authors.initials: C
authors.lastname: Zhou
authors.forename: Zhang-pu
authors.initials: ZP
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Zhe
authors.initials: Z
authors.lastname: Feng
authors.forename: Xue-ping
authors.initials: XP
authors.lastname: Zhou
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects; D000818:Animals; D001169:Arthritis, Experimental / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005347:Fibroblasts / Q000473:pathology*; D008297:Male; D009000:Monocytes / Q000473:pathology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000473:pathology*
chemical_list: D000276:Adjuvants, Immunologic; D004365:Drugs, Chinese Herbal; C000606145:qingluo tongbi