Detailed Description:

Our group has developed interdisciplinary expertise in biomarkers related to distinct aspects of inflammation-induced joint damage, most notably those associated with degradation of components of the extracellular matrix, bone loss, or associated with post-translational changes on protease inhibitors. The objectives of this group project is to collect SF and paired sera and carry out preclinical studies to evaluate, alone or by combination testings, the potential of novel biomarkers for their prevalence and diagnostic/prognostic values in patients with arthritis, and to determine how therapeutic intervention regulate their levels. More specifically, we will study (1) biomarkers associated with osteoclastic bone resorption and synthesis/degradation of cartilage, (2) inhibitors of enzymes (calpastatin) that are preferentially targeted by rheumatoid patients, as well as (3) enzymes (e.g. Matrix Metalloproteinases (MMPs)) responsible for the cleavage of components of the articular cartilage. Finally, we propose to characterize the repertoire of specific active proteases in the SF of arthritic patients concomitantly to the use biomarkers (neoepitopes of cleaved collagens) previously associated with cartilage destruction and synthesis to identify new targets for the development of protease inhibitors for the treatment of arthritis. Furthermore, our project will also provide the opportunity to test the potential of measuring the net proteolytic activity by Fluorescent-Activated Substrate Conversion as a method of monitoring disease activity and treatment efficiency in a clinical setting.}}