Anti-arthritic Action Mechanisms of Natural Chondroitin Sulfate in Human Articular Chondrocytes and Synovial Fibroblasts

被引：41
作者：
Imada, Keisuke [1 ]
Oka, Hideki [2 ]
Kawasaki, Daisuke [2 ]
Miura, Naoyoshi [2 ]
Sato, Takashi [1 ]
Ito, Akira [1 ]
机构：
[1] Tokyo Univ Pharm & Life Sci, Dept Biochem & Mol Biol, Sch Pharm, Tokyo 1920392, Japan
[2] Zena Pharmaceut Co Ltd, Consumer Healthcare Labs, Cent Res Labs, Kumagaya, Saitama 3600111, Japan
来源：
BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2010年 / 33卷 / 03期
关键词：
chondroitin sulfate; tissue inhibitor of metalloproteinase; aggrecanase; cartilage; chondrocyte; synovial fibroblast; COLLAGEN-INDUCED ARTHRITIS; KNEE OSTEOARTHRITIS; MATRIX-METALLOPROTEINASE; CARTILAGE DEGRADATION; TISSUE INHIBITOR; GENE-EXPRESSION; TNF-ALPHA; AGGRECAN; INTERLEUKIN-1-BETA; IDENTIFICATION;
D O I：
10.1248/bpb.33.410
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
To clarify the exact anti-arthritic action mechanisms of chondroitin sulfate (CS), we evaluated the effects of CS derived from shark cartilage (CS-SC) composed mainly of chondroitin-6-sulfate and porcine trachea cartilage (CS-PC) composed mostly of chondrotin-4-sulfate on the functions of human articular chondrocytes and synovial fibroblasts. Both CS-SC and CS-PC (from 1 to 100 mu g/ml) effectively suppressed the interleukin (10 ng/ml)-enhanced gene expression of aggrecanase-1/a disintegrin and nietalloproteinase with thrombospondin-like motifs (ADAMTS)-4 and aggrecanase-2/ADAMTS-5 in articular chondrocytes embedded in alginate beads and synovial fibroblasts. In addition, CS-SC and CS-PC overcame the 1L-1 beta-mediated suppression of the aggrecan core protein mRNA, and suppressed the 1L-1 beta-enhanced collagenase-3/matrix metalloproteinase (MMP)-13 gene expression in chondrocytes. CS-PC, but not CS-SC effectively recovered file 1L-1 beta-reduced gene expression of tissue inhibitor of metalloproteinases (TIMP)-3 in chondrocytes. and enhanced the production of TIMP-1 in synovial fibroblasts. It is noteworthy that CS is able to modulate the function of synovial fibroblasts as well as that of chondrocytes. Therefore, CS is very likely to he multifunctional chondroprotective material for degenerative arthritic diseases.
引用
收藏
页码：410 / 414
页数：5
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