Extracellular Matrix Remodelling-Proteoglycan and collagen turnover in arthritis

Rheumatoid arthritis is a chronic, inflammatory and systemic disease characterised by joint destruction and pannus formation. To enlarge the understanding how pannus and granulation tissue are formed two animal models were used; one using cartilage wrapped in cotton and implanted into a rat air pouch (AP) and one where mBSA induced arthritis (AIA) was performed. Cell cultures from synovial specimens were established and their significance in matrix production was evaluated. In the AP model the development new tissue was studied whereas in the AIA model remodelling of existing tissue occurred. In both animal models the cartilage undergoes destruction and thereby releases aggrecan. In the AIA model the cartilage remodelled over time. Here an increased amount of biglycan was seen early which was followed by an increased amount of collagen and decorin. This lead to a more fibrous cartilage with changed properties. When the cartilage was removed from its original place and implanted into the air pouch this phenomenon was not seen. Instead, a stable level of collagen was noted throughout the study and only 20% aggrecan remained. In pannus and in cotton, the same type of changes occurred. Versican and aggrecan were the first proteoglycans to appear in the tissue, thereafter an increase in the level of biglycan at the peek of inflammation. Also the trisomic cultures started producing versican, which was 4-fold elevated compared to the disomic cultures. Aggrecan leaking out of the degrading cartilage affects the development of the surrounding ECM, by sustaining the inflammation and thereby delaying the ECM formation. At later stages of the arthritis, elevated levels of collagen and decorin occurred. The increase in collagen correlated with the appearance of myofibroblasts. All these findings indicate an intricate interplay between cartilage and its surrounding.