Disruption of circadian rhythm aggravates experimental arthritis: study in cry gene-knockout mice.

昼夜节律的破坏会加剧实验性关节炎：对 cry 基因敲除小鼠的研究。

• 批准号: 18591110
• 负责人: HASHIRAMOTO Akira
• 金额: $ 2.44万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591110/
• 关键词: circadian rhythum; Cry gene; rheumatoid arthritis; TNF-a; Cry; TNF-a; 関節炎; 時計遺伝子

Mammalian clock genes, Per and Cry, physiologically regulate circadian rhythm. We show that experimental arthritis in mice impairs rhythmic expression of Per and Cry, and deletion of Cry further aggravates arthritis to maximal levels. While Wee-1 kinase and c-Fos/ AP-1, a transactivator of Wee-1, are up-regulated in human rheumatoid arthritis (RA), and Wee-1 is the sole molecule up-regulated among cell cycle regulators in Cry-1/2 deficient mice, the splenic T cells of Cry-1/2 deficient mice were activated, and the molecules playing essential roles in arthritis such as c-Fos/AP-1, Wee-1, inflammatory cytokines including TNF-a, IL-lb and IL-6, and matrix-degrading MMP-3 were all increased. In particular, Cry transactivated pro-inflammatory cytokine TNF-a. Thus, biological clock modulates human health and disease, in particular, arthritis

哺乳动物的生物钟基因Per和Cry在生理上调节昼夜节律。我们发现实验性关节炎小鼠损伤了Per和Cry的节律性表达，而Cry的缺失进一步加重了关节炎的最大程度。在类风湿关节炎（RA）中，Wee-1激酶和Wee-1的反激活因子c-Fos/AP-1上调，而在ry-1/2缺陷小鼠中，Wee-1是细胞周期调节因子中唯一上调的分子，而在ry-1/2缺陷小鼠中，脾脏T细胞被激活，在关节炎中起重要作用的分子如c-Fos/AP-1、Wee-1、炎症细胞因子如TNF-a、IL-lb和IL-6以及基质降解MMP-3均升高。特别是，Cry反激活了促炎细胞因子TNF-a。因此，生物钟调节着人类的健康和疾病，尤其是关节炎

项目成果

Anchorage on fibronectin via VIA-5(a5b1 integrin)protects rheumatoid synovialcells from Fas-induced apoptosis

通过 VIA-5​​（a5b1 整合素）锚定在纤连蛋白上可保护类风湿滑膜细胞免受 Fas 诱导的细胞凋亡

• 发表时间: 2006
• 期刊: Ann Rheum Dis 65(6)
• 作者: Kitagawa;A;Miura;Y;Saura;R;Mitani;M;Ishikawa;H;Hashiramoto;A;Yoshiya;S;Shiozawa;S;Kurosakam M
• 通讯作者: Kurosakam M

Heat Schock Protein90はインテグリンを介して関節リウマチ滑膜細胞のシグナル伝達に作用する

Heat Schock Protein 90 通过整合素作用于类风湿性关节炎滑膜细胞的信号转导

• 发表时间: 2006
• 作者: 柱本照;川添高子;吉田幸祐;阿部修治;中川夏子;三枝康宏;塩沢和子;石川斎;塩沢俊一
• 通讯作者: 塩沢俊一

Decoy receptor 3 expressed in rheumatoid synovial fibroblasts protects the cells against fas-induced apoptosis

• DOI: 10.1002/art.22494
• 发表时间: 2007-04-01
• 期刊: ARTHRITIS AND RHEUMATISM
• 作者: Hayashi, Shinya;Miura, Yasushi;Doita, Minoru
• 通讯作者: Doita, Minoru

Variant Death Receptor 3 Gene, Genetically Associated with Rheumatoid Arthritis Inhibit TL1A-induced Splenocyte Signaling and CD4/8 Cell Subset in Thymus

与类风湿关节炎遗传相关的变异死亡受体 3 基因抑制 TL1A 诱导的脾细胞信号传导和胸腺中的 CD4/8 细胞亚群

• 发表时间: 2007
• 作者: Kawazoe T;Hashiramoto A;Tsumiyama K;Shiozawa S,
• 通讯作者: Shiozawa S,

RAにおける睡眠障害と関節炎

RA 中的睡眠障碍和关节炎

• 发表时间: 2007
• 作者: Kawazoe T;Hashiramoto A;Tsumiyama K;Shiozawa S,;柱本照
• 通讯作者: 柱本照