Anti-arthritic Action Mechanisms of Natural Chondroitin Sulfate in Human Articular Chondrocytes and Synovial Fibroblasts
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概要
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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 μg/ml) effectively suppressed the interleukin (IL)-1β (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-1β-mediated suppression of the aggrecan core protein mRNA, and suppressed the IL-1β-enhanced collagenase-3/matrix metalloproteinase (MMP)-13 gene expression in chondrocytes. CS-PC, but not CS-SC effectively recovered the IL-1β-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.
著者
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ITO Akira
Department of Physics, The Cancer Institute, Japanese Foundation for Cancer Research
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SATO Takashi
Department of Neurosurgery, University of Yamanashi, Faculty of Medicine
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IMADA Keisuke
Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy a
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Oka Hideki
Consumer Healthcare Laboratories, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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Kawasaki Daisuke
Consumer Healthcare Laboratories, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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Miura Naoyoshi
Consumer Healthcare Laboratories, Central Research Laboratories, Zeria Pharmaceutical Co., Ltd.
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Ito Akira
Department Of Biochemistry And Molecular Biology School Of Pharmacy Tokyo University Of Pharmacy And
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Sato Takashi
Department Of Internal Medicine And Clinical Immunology Yokohama City University School Of Medicine
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Sato Takashi
Department Of Communications And Computer Engineering Kyoto University
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Sato Takashi
Department Of Applied Biochemistry And Food Science Saga University
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