RAGE and activation of chrondrocytes and fibroblast-like synoviocytes in joint diseases

This dissertation describes a new model in which cartilage degradation can be studied. New cartilage is formed by bovine chondrocytes obtained from the slaughterhouse and cocultured with synovial cells from rheumatoid arthritis (RA) patients to study the interaction between the chondrocytes and synoviocytes.The results of our study show that the role of synoviocytes in cartilage degradation is dependent on the presence of live chondrocytes. In osteoarthritis (OA) patients an increased level of advanced glycation endproducts (AGEs), which can bind to the receptor for AGEs (RAGE), is found in the cartilage. In RA patients, increased levels of AGEs and other RAGE-binding proteins is found in serum, synovial tissue and –fluid. We therefore studied the effect of RAGE activation on chondrocytes and synoviocytes from OA and RA patients and found that both chondrocytes and synoviocytes become more active and start to degrade cartilage. Blockade of RAGE activation might therefore be an interesting target in treatment of OA and RA patients. The synoviocytes in RA synovial tissue have an altered, aggressive phenotype and can degrade cartilage. Hereby, they share properties of fibrotic/tumorigenic cells. We found that healthy synoviocytes are epithelial-like cells and that synovial fluid from RA patients will induce a change in phenotype and production of proteins found in fibrotic/tumorigenic cells. BMP-7, a protein able to induce cartilage production by chondrocytes, is able to inhibit this change in phenotype and might therefore be an interesting target to prevent the alteration of synoviocyte phenotype.</p

Fibroblast-like synoviocyte-chondrocyte interaction in cartilage degradation

Objective: In vitro models for joint diseases often focus on a single cell type, such as chondrocytes in osteoarthritis (OA) or fibroblast-like synoviocytes (synoviocytes) in rheumatoid arthritis (RA). However, these joint diseases affect the whole joint and interaction between chondrocytes and synoviocytes may play an important role in disease pathology. The current study was designed to study the use of the alginate recovered chondrocyte method as a model for cartilage degradation and to study interaction between chondrocytes and synoviocytes. Methods: Bovine chondrocytes were cultured in alginate beads for 1 week, subsequently chondrons were retrieved and seeded into transwells. Every two days cartilage-slices were analysed for proteoglycan content (colorimetric, Blyscan GAG kit), collagen content (HPLC) and collagen HP and LP crosslinking (HPLC). For degradation experiments, monocultures of cartilage-slices labelled with 35S and cocultures with synoviocytes were stimulated with IL-1β or TNF-α. After 7 days, 35S release was measured taken as a measure of cartilage degradation. Results: After biochemical analysis, three week old cartilage-like slices were chosen to perform cartilage-degradation experiments. Synoviocytes were able to induce cartilage degradation only in the presence of living chondrocytes. In addition, the cytokines interleukin 1 (IL-1β) and tumor necrosis factor (TNF-α) were only able to induce cartilage degradation by chondrocytes, not by synoviocytes. Conclusion: These data indicate that the alginate recovered chondrocyte method provides a novel model for cartilage degradation in which the interaction between synoviocytes and chondrocytes can be studied. © Copyright Clinical and Experimental Rheumatology 2007