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 mug/ml) effectively suppressed the interleukin (IL)-1beta (10 ng/ml)-enhanced gene expression of aggrecanase-1/a disintegrin and metalloproteinase 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 IL-1beta-mediated suppression of the aggrecan core protein mRNA, and suppressed the IL-1beta-enhanced collagenase-3/matrix metalloproteinase (MMP)-13 gene expression in chondrocytes. CS-PC, but not CS-SC effectively recovered the IL-1beta-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 be multifunctional chondroprotective material for degenerative arthritic diseases.
Imada
Keisuke
K
Department of Biochemistry and Molecular Biology, Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Hachioji, Tokyo 192-0392, Japan. imadak@toyaku.ac.jp
Oka
Hideki
H
Kawasaki
Daisuke
D
Miura
Naoyoshi
N
Sato
Takashi
T
Ito
Akira
A
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002356:Cartilage; D002358:Cartilage, Articular / Q000187:drug effects*; D019902:Chondrocytes / Q000187:drug effects*; D002809:Chondroitin Sulfates / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects*; D015870:Gene Expression; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D010003:Osteoarthritis / Q000188:drug therapy; D020011:Protective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D012754:Sharks; D013552:Swine; D013583:Synovial Membrane / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics / Q000378:metabolism
D053583:Interleukin-1beta; D020011:Protective Agents; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019717:Tissue Inhibitor of Metalloproteinase-3; D002809:Chondroitin Sulfates; D051722:ADAM Proteins; D053509:Matrix Metalloproteinase 13