Grant: Operating Grant - PA: Musculoskeletal Health, Arthritis, Skin and Oral Health

Rheumatoid arthritis leads to rapid destruction of cartilage and bone in a large proportion of patients, leading to severe functional disabilities. The molecular mechanisms underlying disease severity and destructive progression are poorly characterized, but are certainly key factors to identify patients who may benefit from early aggressive treatments and to find more effective ways to treat and prevent joint destruction. A population of cell lining the articulation, the synovial cells, was shown to be key to invasive joint destruction by producing enzymes that cause permanent cartilage damage. While studying synovial cells, we made the original observation that their ability to degrade cartilage was due to the formation of specialized membrane protrusion similar to the invadopodia (or invasive foot processes) made by cancer cells. These structures concentrate enzymes, which are particularly powerful at inducing joint damage. Importantly, interference with the formation of invadopodia structures in an animal model of arthritis efficiently prevented joint damages. Our study will focus on the understanding of the molecules and genes involved in the production of these invasive structures and to know how they get turned on. Our aim is to identify new mechanisms involved in cartilage degradation and to use some of the key molecules involved as molecular targets and prognostic markers for patients experiencing rapid joint degradation and who are most in need of timely aggressive treatment.