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Mechanism of bone and joint destruction in rheumatoid arthritis. Effect of mechanical stress on synovial cells.

类风湿关节炎中骨和关节破坏的机制。

基本信息

批准号：
15591588
负责人：
SHUTO Toshihide
金额：
$ 2.24万
依托单位：
KYUSHU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

Synovial tissue is believe to be a main site of inflammation in rheumatoid arthritis (RA). Synovial tissue exists to line joint capsule, so the tissue is expand or relaxed in accordance with joint motion. That suggests synovial tissue is exposed to mechanical stress, however, the effect of mechanical stress on synovial tissue is not well understood. We used Flexercell system to apply expansile stress on synovial cells. Rheumatoid synovial cells seeded on type I collagen-coated flexible-bottomed well changed the shape in response to the mechanical stress. Mechanical stress induces intracellular signaling which involves small GTP protein, Rho, Rac, Ras pathway. Aminobisphosphonate, alendronate, inhibits prenylation of the small GTP protein, retards progression of bone erosion in RA patients. The RA patients who intake alendronate are tend to less susceptible to bone and joint destruction in hip and knee joints. To examine the relationship between the direction of mechanical stress and site of marginal erosion formation. More erosion is likely to be formed in ulnar side of first finger and radial side of second finger. Ulnar side of first finger and radial side of second finger are thought to be more susceptible to expansile stress. Synovial tissue lining around tendon is also susceptible to expansile mechanical stress. Cultured synovial cells differentiated to osteoclast-like cells, which formed resorption pits on dentine slice. Synovial cells derived from tendon sheath expressed MMP-1,2,3,13 and TIMP-1,2. Moreover, the cells also expressed TNF-α, IL-1β, IL-6 and RANKL. It is suggested that mechanical stress stimulates synovial cells to express pro-inflammatory cytokine and RANKL, as well as MMPs, thereby enhancing not only synovial inflammation, but joint destruction.

滑膜组织被认为是类风湿性关节炎（RA）炎症的主要部位。滑膜组织存在于关节囊内，因此组织根据关节运动而扩张或松弛。这表明滑膜组织暴露于机械应力，然而，机械应力对滑膜组织的影响尚不清楚。我们使用 Flexercell 系统对滑膜细胞施加膨胀应力。接种在 I 型胶原涂层柔性底部孔上的类风湿滑膜细胞会响应机械应力而改变形状。机械应力诱导细胞内信号传导，涉及小 GTP 蛋白、Rho、Rac、Ras 通路。氨基二膦酸盐、阿仑膦酸盐可抑制小 GTP 蛋白的异戊二烯化，延缓 RA 患者骨侵蚀的进展。服用阿仑膦酸钠的 RA 患者往往不太容易受到髋关节和膝关节的骨和关节破坏。检查机械应力方向与边缘侵蚀形成位置之间的关系。第一指的尺侧和第二指的桡侧容易形成较多的糜烂。人们认为第一手指的尺侧和第二手指的桡侧更容易受到膨胀应力的影响。肌腱周围的滑膜组织内壁也容易受到膨胀机械应力的影响。培养的滑膜细胞分化为破骨细胞样细胞，在牙本质切片上形成吸收凹坑。源自腱鞘的滑膜细胞表达MMP-1,2,3,13和TIMP-1,2。此外，细胞还表达TNF-α、IL-1β、IL-6和RANKL。研究表明，机械应力刺激滑膜细胞表达促炎细胞因子和 RANKL 以及 MMP，从而不仅增强滑膜炎症，而且增强关节破坏。

项目成果

期刊论文数量（34）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Coonrad-Morrey total elbow arthroplasty

Coonrad-Morrey 全肘关节置换术

DOI：
发表时间：
2006
期刊：
Bone, joint, Ligament 18(7)
影响因子：
0
作者：
首藤敏秀;Toshihide Shuto
通讯作者：
Toshihide Shuto

Diagnosis of reactive arthritis and DMARDs therapy for chronic cases.

反应性关节炎的诊断和慢性病例的 DMARD 治疗。

DOI：
发表时间：
2005
期刊：
Clinical Rheumatology 17(1)
影响因子：
0
作者：
首藤敏秀;Toshihide Shuto;Toshihide Shuto;Toshihide shuto;Satoshi Ikemura;Kenjiro Nishida;首藤敏秀;Toshihide Shuto;Toshihide Shuto
通讯作者：
Toshihide Shuto

反応性関節炎の診断と慢性化例に対するDMARDs療法

反应性关节炎的诊断和慢性病例的 DMARD 治疗

DOI：
发表时间：
2005
期刊：
臨床リウマチ 17(1)
影响因子：
0
作者：
首藤敏秀;Toshihide Shuto;Toshihide Shuto;Toshihide shuto;Satoshi Ikemura;Kenjiro Nishida;首藤敏秀;Toshihide Shuto;Toshihide Shuto;Satoshi Ikemura;Toshihide Shuto;Toshihide Shuto;首藤敏秀
通讯作者：
首藤敏秀

Rheumatoid arthritis