1998 Fiscal Year Final Research Report Summary
EFFECTS OF AGING ON THE METABOLISM OF PROTEOGLYCANS IN ARTICULAR CHONDROCYTE
| Project/Area Number |
09835011
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
老化(加齢)
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| Research Institution | TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCE |
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Principal Investigator |
ITO Akira TOKYO UNIVERSITY OF PHARMACY AND LIFE SCIENCE,SCHOOL OF PHARMACY,DEPARTMENT OF BIOCHEMISTRY,PROFESSOR, 薬学部, 教授 (70096684)
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| Project Period (FY) |
1997 – 1998
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| Keywords | AGING / CHONDROCYTES / MATRIX METALLOPROTEINASES / RHEUMATOID ARTHRITIS / OSTEOARTHRITIS / HUMAN URINARY TRYPSIN INHIBITOR / NOBILETIN / DIHYDROXYCOUMARIN |
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| Research Abstract |
The relationship between aging and destruction of articular cartilage in rheumatoid arthritis (RA) and osteoarthritis (QA) was investigated using rabbit articular chondrocytes. Growth rate and proteoglycan synthesis in aged chondrocytes prepared from 1.5 years old were significantly lower than in the cells from 3 weeks and 6 months old rabbits. When the aged cells were treated with interleukin lalpha (IL-1alpha) the production of matrix metalloproteinases (MMPs) and concomitant release of proteoglycan were induced. These results strongly suggested that MMPs play an essential role in the destruction of proteoglycans and the suppression of MMPs as well as prostaglandins(PGs)is very likely to be effective to suppress the RA and OA.
From this point of view, effects of urinary trypsin inhibitor (UTI), dihydroxycoumarin and citrus flavonoid of nobiletin on the activation and production of proMMPs in rabbit chondrocytes were investigated. UTI effectively inhibited the plasminogen activator-mediated activation of plasminogen in rabbit chondrocytes co-treated with IL-1alpha and plasminogen, and eventually suppressed the activation of proMMP-1/procollagenase and proMMlP-3/prostromelysin and the release of proteoglycans. Both dihydroxycoumarin and nobiletin effectively suppressed the IL-1alpha-mediated production of proMMPs-1 and -3 in rabbit chondrocytes and synovial cells. Nobiletin also down-regulated the production of PGE2 in rabbit chondrocytes and synovial cells. Therefore, these three agents exert desirable effects on the maintenance of articular cartilage in RA and OA, and are novel candidate for the above forms of arthritis.
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[Publications] H.Yamada, K.Watanabe, T.Saito, H.Hayashi, Y.Niitani, T.Kikuchi, A.Ito, and L.S.Lohmander: "Esculetin (dihydroxycoumarin) inhibits the production of matrix metalloproteinases in cartilage explants, and oral administration of its prodrug, CPA-926, suppresses the cartilage detruction in rabbit experimental osteoarthritis" Journal of Rheumatology. 26(印刷中). (1999)
Description
「研究成果報告書概要(和文)」より
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[Publications] Harumoto Yamada, Koju Watanabe, Tsuyoshi Saito, Haruhisa Hayashi, Toshiyuki Kikuchi, Yoshiaki Niitani, Akira Ito, Kyosuke Fujikawa and L.Stefan Iohmander: "Esculetin (dihydroxycoumarin) inhibits the production of matrix metalloproteinases in cartilage explants, and oral administration of its prodrug, CPA-926, suppresses cartilage destruction in rabbit experimental osteoarthritis." Journal of Rheumatology. 26 (in press). (1999)
Description
「研究成果報告書概要(欧文)」より
