The mechanical functions of joints depend on strict separation of the compartment borders. Crossing of the joint compartment boundaries and destruction of the cartilage compartment is found in inflammatory and degenerative joint diseases such as rheumatoid arthritis and osteoarthritis. We hypothesise that there are molecular cues at the joint compartment borders maintaining the integrity of these borders. Candidate molecules for this function are repellent factors, which are expressed in fetal and adult synovial tissue and cartilage. The principal purpose of this proposal is to single out candidate repellent factors that may exert the function of establishing and maintaining tissue boundaries by the use of expression studies and functional studies. The cell types under scrutiny are synovial fibroblasts as potential invaders and chondrocytes as cells that may exert repellent activities. Their potential to produce repellent factors and react to repellent factors will be studied in vitro in different model systems. Pathways regulating the expression of repellent factors and molecules possibly executing repellent activities will be studied in vitro and in vivo.
