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

关节边界（滑膜组织、软骨/骨）的细胞-细胞和细胞-基质相互作用对炎症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，并对关节表面的破坏起重要作用。这个项目的目的是表征细胞-基质相互作用在滑膜组织进入软骨的侵入性边界。在第一阶段，研究粘附分子在该边界的表达谱（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，雌激素、黄体酮和睾酮对整合素表达的影响将被评估。在第二阶段，将检查在第一阶段确定的在激素影响下上调或下调整合素表达的调节对基质降解的影响，包括评估整合素表达调节后细胞信号传导的改变。

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.