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

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.