Thrombin and mast cell tryptase are trigger proteases in arthritis.

凝血酶和肥大细胞类胰蛋白酶是关节炎的触发蛋白酶。

基本信息

  • 批准号:
    17591577
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

The purpose of this study is to clarify the pathophysiological significance of thrombin and mast cell tryptase in articular lesions of patients with rheumatoid arthritis (RA) and osteoarthritis (OA).We obtained the following results.1. Thrombin and mast cell tryptase (MCT) activity in synovial fluid were significantly higher in RA than in osteoarthritis (OA) and healthy subjects. In synovial tissue, MCT activity was similar in RA and OA.2. There was no significant difference in synovial PAR expression between RA and OA, except for expression of PAR-2 mRNA transcripts3. Thrombin and MCT enhanced the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells.4. Furthermore, PAR-2 activating peptide stimulated the release of IL-8 from synovial fibroblast-like cells, suggesting that mast cell tryptase in synovial fluid stimulates the proliferation of synovial fibroblast-like cells and the release of IL-8 from these cells via activation of PAR-2.5. This study showed that an unglycosylated form of mast cell tryptase accumulated in higher concentration in synovial fluid from RA relative to OA, and that there was higher expression of synovial PAR-2 mRNA transcripts in RA compared with that in OA.In summary, higher secretion of mast cell tryptase and thrombin into synovial fluids in RA relative to OA stimulates higher proliferation of the synovium and production of proinflammatory cytokine in SFCs in RA compared with OA.
本研究旨在阐明凝血酶和肥大细胞胰蛋白酶在类风湿关节炎(RA)和骨关节炎(OA)患者关节病变中的病理生理意义。我们得到了以下结果。RA患者滑液中凝血酶和肥大细胞胰蛋白酶(MCT)活性明显高于骨关节炎(OA)和健康人。在滑膜组织中,RA和oa的MCT活性相似。RA与OA滑膜PAR的表达差异无统计学意义,但PAR-2 mRNA转录量存在差异。凝血酶和MCT增强滑膜成纤维细胞样细胞的增殖和这些细胞IL-8的释放。此外,PAR-2激活肽刺激滑膜成纤维细胞样细胞释放IL-8,表明滑膜液中的肥大细胞胰蛋白酶通过激活PAR-2.5刺激滑膜成纤维细胞样细胞的增殖和这些细胞释放IL-8。本研究表明,与OA相比,RA的滑膜液中积累了更高浓度的非糖基化形式的肥大细胞胰蛋白酶,RA的滑膜PAR-2 mRNA转录物的表达高于OA。综上所述,与OA相比,RA中滑膜液中肥大细胞胰蛋白酶和凝血酶的分泌增加,刺激了RA中sscs中滑膜的增殖和促炎细胞因子的产生。

项目成果

期刊论文数量(18)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Distinct expression of mast cell tryptase and protease activated receptor-2 in synovia of rheumatoid arthritis and osteoarthritis
  • DOI:
    10.1007/s10067-006-0495-8
  • 发表时间:
    2007-08-01
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Nakano, Shunji;Mishiro, Takuya;Yasui, Natsuo
  • 通讯作者:
    Yasui, Natsuo
Association between single-nucleotide polymorphisms in the SEC8L1 gene, which encodes a subunit of the exocyst complex, and rheumatoid arthritis in a Japanese population
  • DOI:
    10.1002/art.21013
  • 发表时间:
    2005-05-01
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Hamada, D;Takata, Y;Itakura, M
  • 通讯作者:
    Itakura, M
Osteoactivin upregulates expression of MMP-3 and MMP-9 in fibroblasts infiltrated into denervated skeletal muscle in mice
Total hip arthroplasty in osteopetrosis using computer-assisted fluoroscopic navigation
  • DOI:
    10.1016/j.arth.2005.03.037
  • 发表时间:
    2005-12-01
  • 期刊:
  • 影响因子:
    3.5
  • 作者:
    Egawa, H;Nakano, S;Yasui, N
  • 通讯作者:
    Yasui, N
Treatment of knee osteoarthritis associated with extraarticular varus deformity of the femur: staged total knee arthroplasty following corrective osteotomy
  • DOI:
    10.1007/s00776-006-1035-8
  • 发表时间:
    2006-07-01
  • 期刊:
  • 影响因子:
    1.7
  • 作者:
    Yagi, Keisuke;Matsui, Yoshito;Yasui, Natsuo
  • 通讯作者:
    Yasui, Natsuo
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NAKANO Shunji其他文献

NAKANO Shunji的其他文献

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{{ truncateString('NAKANO Shunji', 18)}}的其他基金

Establishment of bilateral asymmetry through selective segregatin of sister chromatids
通过姐妹染色单体的选择性分离建立双侧不对称
  • 批准号:
    24770204
  • 财政年份:
    2012
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Clarification of the pathophysiological significance of mast cell tryptase and protease activated receptor-2 (PAR-2) in articular destruction
阐明肥大细胞类胰蛋白酶和蛋白酶激活受体 2 (PAR-2) 在关节破坏中的病理生理学意义
  • 批准号:
    15591581
  • 财政年份:
    2003
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
The pathophysiological significance of proteases in patients with chronic inflammatory joint disease
蛋白酶在慢性炎症性关节病患者中的病理生理意义
  • 批准号:
    12671421
  • 财政年份:
    2000
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

相似国自然基金

抑素蛋白(prohibitin)1调控蛋白酶激活受体(protease-activated receptor)1内化转运及降解的功能和机制
  • 批准号:
    31270835
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