Zhuanggu Jianxi Decoction () limits interleukin-1 β-induced degeneration chondrocytes via the caveolin-p38 MAPK signal pathway.
OBJECTIVE
To evaluate the effect of Zhuanggu Jianxi Decoction (, 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-1 β stimulation, the degeneration of CDs was verified by inverted microscope, toluidine blue stain and type II 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, caveolin-1 protein expression and the phosphorylation level of p38 were determined by Western blotting, and the mRNA expression of IL-1 β, tumor necrosis factor α (TNF-α), matrix metalloproteinase 3 (MMP-3) and MMP-13 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-α, MMP-3 and MMP-13. 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.


CONCLUSIONS
ZGJXD can prevent CDs degeneration via inhibition of caveolin-p38 MAPK signal pathway, which might be one of the mechanisms that ZGJXD treats osteoarthritis.
Fujian University of Traditional Chinese Medicine, Fuzhou, 350122, China.
Hu
H
Yan
You-xin
YX
Su
Xue-yi
XY
Lin
Bao-jun
BJ
Chen
Qing
Q
Zhang
Zi-yi
ZY
Zhang
Yi-ru
YR
Wang
Ya-nan
YN
Li
Mei-li
ML
Lu
Zhen
Z
He
Lu
L
Sheng
Wen-ting
WT
Wang
D000818:Animals; D001483:Base Sequence; D015153:Blotting, Western; D022461:Caveolins / Q000378:metabolism*; D019902:Chondrocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D017931:DNA Primers; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D020869:Gene Expression Profiling; D053583:Interleukin-1beta / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
D022461:Caveolins; D017931:DNA Primers; D004365:Drugs, Chinese Herbal; D053583:Interleukin-1beta; D012333:RNA, Messenger; C000594120:zhuanggu jianxi; D048051:p38 Mitogen-Activated Protein Kinases