中山醫學大學機構典藏 CSMUIR:Item 310902500/10500
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    题名: Upregulation of urokinase-type plasminogen activator and inhibitor and gelatinase expression via 3 mitogen-activated protein kinases and PI3K pathways during the early development of osteoarthritis.
    作者: Hsieh YS
    Yang SF
    Lue KH
    Chu SC
    Li TJ
    Lu KH
    贡献者: 中山醫學大學
    日期: 2007-04
    上传时间: 2015-03-18T05:15:43Z (UTC)
    摘要: OBJECTIVE:
    To examine whether upregulation of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1), and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in early knee osteoarthritis (OA) of humans occurs through 3 major mitogen-activated protein kinases (MAPK): extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase signaling pathways, and the phosphatidylinositol 3-kinase (PI3K) signaling pathway.
    METHODS:
    Enzyme linked immunosorbent assay and gelatin zymography were used to investigate the effects of ERK 1/2 inhibitor U0126, JNK and p38 inhibitor SB203580, and PI3K inhibitor LY294002 on the secretion of u-PA, PAI-1, MMP-2, and MMP-9 in early osteoarthritic tissue cultures, with or without interleukin 1alpha (IL-1alpha) and lipopolysaccharide (LPS) induction.
    RESULTS:
    Our findings were: (1) latent and active forms of MMP-9 secretion in synovial and some meniscal cultures were inhibited significantly by U0126, SB203580, and LY294002; (2) latent and active forms of MMP-2 secretion were also inhibited significantly by U0126 and LY294002, but not by SB203580, except for active MMP-2 in synovial cultures; (3) a similar observation was seen in IL-1alpha- and LPS-treated cultures; and (4) U0126, SB203580, and LY294002 significantly decreased u-PA and PAI-1 levels in all cultures in the presence or absence of IL-1alpha and LPS.
    CONCLUSION:
    MAPK ERK, JNK, and p38 signaling pathways and the PI3K signaling pathway are involved in upregulation of u-PA, PAI-1, and gelatinase expression during early development of knee OA. Thus, blocking PA/plasmin and gelatinase expression by novel physiologic and pharmacological inhibitors could be an important therapeutic or preventive approach for early OA.
    URI: https://ir.csmu.edu.tw:8080/ir/handle/310902500/10500
    關聯: J Rheumatol. 2007 Apr;34(4):785-93.
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