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

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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.