Inhibition mechanism of Qingluo Tongbi Granule (清络通痹颗粒) on osteoclast differentiation induced by synovial fibroblast and monocytes co-culture in adjuvant-induced arthritic rats
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To study the mechanism underlying the inhibitory effect of Qingluo Tongbi Granule (清络通痹颗粒, QTG) on osteoclast differentiation in rheumatoid arthritis in rats.
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.
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).
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.
KeywordsQingluo Tongbi Granule rheumatoid arthritis osteoclast differentiation signaling pathway regulation of tumor necrosis factor receptor-associated factor 6/mitogen-activated protein kinase pathways Chinese medicine
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