Objective: To evaluate the effect of Zhuanggu Jianxi Decoction (壮骨健膝方, ZGJXD) on interleukin- 1 β- (IL-1 β- )-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen-...Objective: To evaluate the effect of Zhuanggu Jianxi Decoction (壮骨健膝方, ZGJXD) on interleukin- 1 β- (IL-1 β- )-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen- activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis. Methods: Serum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL- l β-stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type H collagen immunocytochemistry. After IL-1 β-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveoUn-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL- 1β-, tumor necrosis factor ~ (TNF-oL), matrix metalloproteinase 3 (MMP-3) and MMP-β were examined by real-time polymerase chain reaction. Results: IL-1 β- stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 β, TNF-β, MMP-3 and MMP-β. However, the IL-1 β-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs. Conclusion: ZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.展开更多
基金Supported by the National Natural Science Foundation of China(No.81072828)
文摘Objective: To evaluate the effect of Zhuanggu Jianxi Decoction (壮骨健膝方, ZGJXD) on interleukin- 1 β- (IL-1 β- )-induced degeneration of chondrocytes (CDs) as well as the activation of caveolin-p38 mitogen- activated protein kinase (MAPK) signal pathway, investigating the possible molecular mechanism that ZGJXD treats osteoarthritis. Methods: Serum pharmacology was applied in the present study, where ZGJXD was orally administrated to New Zealand rabbits and then ZGJXD containing serum (ZGJXD-S) was collected for following in vitro experiments. CDs were isolated aseptically from New Zealand rabbits and then cultured in vitro. Upon IL- l β-stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type H collagen immunocytochemistry. After IL-1 β-stimulated CDs were intervened with blank control serum, ZGJXD-S, together with or without SB203580 (a specific inhibitor of p38 MAPK) for 48 h, caveoUn-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL- 1β-, tumor necrosis factor ~ (TNF-oL), matrix metalloproteinase 3 (MMP-3) and MMP-β were examined by real-time polymerase chain reaction. Results: IL-1 β- stimulation induced degeneration of CDs, increased caveolin-1 expression and p38 phosphorylation, up-regulated the mRNA level of IL-1 β, TNF-β, MMP-3 and MMP-β. However, the IL-1 β-induced activation of caveolin-p38 signaling and alteration in the expression of p38 downstream target genes were suppressed by ZGJXD-S and/or SB203580 in CDs. Conclusion: ZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.