Panax ginseng C.A. Meyer modulates the levels of MMP3 in S12 murine articular cartilage cell line.
OBJECTIVE
The destruction of cartilage in patients with osteoarthritis occurs due to an imbalance between matrix synthesis and degradation. Cartilage degradation is induced by the activation of matrix metalloproteinases (MMPs). Therefore, this study was conducted to evaluate the cartilage protective effect of Panax ginseng C.A. Meyer (PG).


METHODS
S12 cells were treated with various concentrations of extract of PG and gensenosides Rd and Rb(3) for 3h, after which 10 ng/ml interleukin-1beta (IL-1beta) was added to the culture media. The levels of MMP3 in the conditioned media were then evaluated using an enzyme-linked immunosorbent assay (ELISA). In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) was used to evaluate the mRNA expression of Type II Collagen and Pro-collagenase. Furthermore, Western blot analysis was performed to identify the roles that PG played in the ERK and p38 signaling pathways.


RESULTS
The MMP3 secretion levels of S12 cells were significantly lowered in response to treatment with PG and gensenosides Rd and Rb(3) at a concentration of 100 microg/ml when compared to cells that were treated with IL-1beta. In addition, PG induced the mRNA expression of Type II Collagen dose dependently. Furthermore, phosphorylated p38 and ERK were detected in S12 articular cartilage cell line that was treated with IL-1beta. PG decreased the phosphorylation of p38, but PG did not exert any effect on phospho-ERK.


CONCLUSIONS
These findings indicate that PG and gensenosides Rd and Rb(3) suppress MMP3 secretion and that gensenosides Rd and Rb(3) are the major elements involved in the suppression of MMP3 by PG. Furthermore, the suppression of MMP3 by PG occurs via the inhibition of phospho-p38 activation. Therefore, PG may exert a protective effect against the cartilage degradation of OA.
Shin
Joon-Shik
JS
Jaseng Hospital of Oriental Medicine, Sinsa-dong, Kangnam-gu, Seoul 135-896, Republic of Korea.
Park
Namhee
N
Ra
Jehyeon
J
Kim
Yangseok
Y
Shin
Minkyu
M
Hong
Moochang
M
Kim
Sung-Hoon
SH
Kwon
Ha-Jeong
HJ
Hong
Seon-Pyo
SP
Kim
Jinju
J
Bae
Hyunsu
H
D015153:Blotting, Western; D002358:Cartilage, Articular / Q000166:cytology* / Q000201:enzymology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D024043:Collagen Type II / Q000096:biosynthesis; D004396:Coloring Agents; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D036145:Ginsenosides / Q000032:analysis / Q000494:pharmacology; D007202:Indicators and Reagents; D053583:Interleukin-1beta / Q000494:pharmacology; D007723:Korea; D009682:Magnetic Resonance Spectroscopy; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D008518:Medicine, East Asian Traditional; D005894:Panax / Q000737:chemistry*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013778:Tetrazolium Salts; D013844:Thiazoles; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D024043:Collagen Type II; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D036145:Ginsenosides; D007202:Indicators and Reagents; D053583:Interleukin-1beta; D061965:Matrix Metalloproteinase Inhibitors; D012333:RNA, Messenger; D013778:Tetrazolium Salts; D013844:Thiazoles; C044463:ginsenoside Rb3; D048051:p38 Mitogen-Activated Protein Kinases; D019278:Matrix Metalloproteinase 3; C022616:thiazolyl blue; C049863:ginsenoside Rd