Kiener Hans P, Niederreiter Birgit, Lee David M, Jimenez-Boj Esther, Smolen Josef S, Brenner Michael B
Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts 02115, USA.
Arthritis Rheum. 2009 May;60(5):1305-10. doi: 10.1002/art.24453.
To define the expression pattern of cadherin 11 in the destructive pannus tissue of patients with rheumatoid arthritis, and to determine whether cadherin 11 expression in fibroblast-like synoviocytes controls their invasive capacity.
Cadherin 11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin 11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L cell clones expressing wild-type cadherin 11, mutant cadherin 11, and empty vector-transfected controls. The invasive capacity of L cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin 11-Fc fusion protein or control immunoglobulin was determined in Matrigel invasion assays.
Immunohistochemical analysis revealed that cadherin 11 is abundantly expressed in cells at the cartilage-pannus junction in rheumatoid synovitis. Assays to determine invasion demonstrated a 2-fold increased invasive capacity of cadherin 11-transfected L cells compared with L cells transfected with E-cadherin or control vector. The invasive behavior of L cells stably transfected with a cadherin 11 construct that lacked the juxtamembrane cytoplasmic domain was diminished to the level of vector control L cells. Furthermore, treatment with the cadherin 11-Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes.
The results of these in vitro studies implicate a role for cadherin 11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis.
确定钙黏蛋白11在类风湿关节炎患者破坏性血管翳组织中的表达模式，并确定成纤维样滑膜细胞中钙黏蛋白11的表达是否控制其侵袭能力。
采用免疫组织化学法评估类风湿滑膜组织中钙黏蛋白11的表达。为了研究钙黏蛋白11在调节成纤维样滑膜细胞侵袭行为中的作用，我们构建了表达野生型钙黏蛋白11、突变型钙黏蛋白11的L细胞克隆以及空载体转染对照。在基质胶侵袭试验中测定L细胞转染子和用钙黏蛋白11-Fc融合蛋白阻断剂或对照免疫球蛋白处理的培养成纤维样滑膜细胞的侵袭能力。
免疫组织化学分析显示，钙黏蛋白11在类风湿滑膜炎软骨-血管翳交界处的细胞中大量表达。侵袭试验表明，与转染E-钙黏蛋白或对照载体的L细胞相比，转染钙黏蛋白11的L细胞侵袭能力增加了2倍。稳定转染缺失近膜胞质结构域的钙黏蛋白11构建体的L细胞的侵袭行为减弱至载体对照L细胞的水平。此外，用钙黏蛋白11-Fc融合蛋白处理可降低成纤维样滑膜细胞的侵袭能力。
这些体外研究结果表明钙黏蛋白11在促进细胞侵袭中起作用，并有助于深入了解慢性滑膜炎和成纤维样滑膜细胞在类风湿关节炎中的侵袭特性。
