Adhesion mechanisms and cellular interactions at the articular borders under the influence of estrogens and dihydrotestosterone

雌激素和二氢睾酮影响下关节边界的粘附机制和细胞相互作用

• 批准号: 27911526
• 负责人: Professor Dr. Ulf Müller-Ladner
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin I
• 依托单位国家: 德国
• 项目类别: Research Units
• 财政年份: 2006
• 资助国家: 德国
• 起止时间: 2005-12-31 至 2009-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/27911526?language=en
• 关键词: Adhesion; mechanisms; cellular; interactions; articular

Cell-cell- and cell-matrix-interactions at articular borders (synovial tissue ¿ cartilage/bone) are essential for the degree and the course of inflammatory joint diseases. Activated synovial fibroblasts in rheumatoid arthritis (RASF) adhere to and invade into adjacent cartilage and bone and contribute significantly to the destruction of articular surfaces. The objective of this project is to characterise cell-matrix interactions at the invasive border of the synovial tissue into cartilage. In phase I, the expression profile of adhesion molecules at this border is investigated (has already been started). Integrins as specific mediators of cell-matrix interactions are in the focus of this investigation. Integrins exhibit functions in almost every cellular biological process and are regulated by diverse extracellular stimuli including hormones. Additionally, the influence of estrogens, progesterone and testosterone will be evaluated with respect to the expression of integrins. In phase II, the impact of the modulation of expression of integrins identified in phase I as up- or downregulated under the influence of hormones on matrix degradation will be examined, including the evaluation of altered cell signalling after the modulation of integrin expression.

关节边界（滑膜组织、软骨/骨）的细胞-细胞和细胞-基质相互作用对于炎性关节疾病的程度和病程至关重要。类风湿性关节炎（RASF）中活化的滑膜成纤维细胞粘附并侵入邻近的软骨和骨，并显著促进关节表面的破坏。本项目的目的是研究滑膜组织进入软骨的侵袭性边界处的细胞-基质相互作用。在第一阶段，粘附分子在这个边界的表达谱进行了研究（已经开始）。整合素作为细胞-基质相互作用的特异性介质是本研究的重点。整合素在几乎所有细胞生物学过程中都发挥作用，并受到包括激素在内的多种细胞外刺激的调节。此外，将评价雌激素、孕酮和睾酮对整联蛋白表达的影响。在II期，将检查在I期中鉴定为在激素对基质降解的影响下上调或下调的整合素表达的调节的影响，包括在整合素表达调节后改变的细胞信号传导的评价。