Investigation on the endogenous annexin 1 system in inflammatory arthritis. (360G-Wellcome-083551_Z_07_Z)

The aim of this project is to dissect the mechanisms behind the inhibitory role of endogenous Annexin 1 (AnxA1) in inflammatory arthritis. We propose to evaluate the impact of the AnxA1 system both from a functional and a morphological point of view, and by assessing its translational potential. The working hypothesis is that a down-regulation or malfunctioning of the AnxA1 system within the arthritic joint contributes to disease progression. This hypothesis will be challenged by integrated analyses in the KxB/N model of arthritis, thereby: i) Comparing the inflammatory response in AnxA1 null mice versus wild type animals; ii) Monitoring the appearance and disposition of the AnxA1 gene by RT-PCR (in wild type animals) and immunohistochemistry (in the AnxA1 null mice) in the joint. Monitoring expression of the AnxA1 receptor(s) by RT-PCR. iii) Testing the effect of glucocorticoids in the two genotypes, as well as the effect of local delivery of a bioactive fragment of the protei n. iv) Assessing the translational impact of this line of research, using the chimaeric SCID mouse model with fragments of human synovial tissue from rheumatoid arthritis patients.