Molecular Mechanisms of Synovial Invasion and Articular Cartilage Damage

Angiogenesis is an early event in arthritis, dependent on endothelial cell (EC) mitosis, migration, and organisation of primitive angiotubes.  In arthritis, the new vessel network MMand leukocyte extravasation transforms synovial tissue (ST) into an aggressive tumor-like ‘pannus’ mediating cartilage destruction. We have previously shown that distinct vascular morphologic phenotypes exist between different arthropathies, effects that impact on level of joint erosion. This programme links imaging technology (arthroscopic, PET/ MRI imaging) with several culture models – synoviocytes, endothelial cells, ex vivo whole tissue synovial explant models and co-culture models with chondrocytes and cartilage explants. The mechanistic effects of potential novel targets (cytokines, growth factor, signalling pathways) on angiogenesis, migration/invasive mechanisms, cartilage degradation and bone resorption are examined. Key signalling pathways involved in dictating vessel sprouting, vessels stability, cytoskeletal rearrangement, extracellular matrix degradation and osteoclastogenesis are being examined, with a focus on distinct pathogenic phenotypes.

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