Tissue destruction in arthritis : experimental studies

Sammanfattning: Destruction of joint cartilage and bone is one of the most serious consequences of chronic arthritis. Clinically, the standard assessment of joint destruction is performed by radiography. The sensitivity of radiographic analysis is rather poor, however, and destructive reactions have usually been ongoing for 3-6 months before erosions become radiologically visible. This thesis addresses the potential use of biological molecules, i.e. COMP (cartilage oligomeric matrix protein) and BSP (bone sialoprotein), and their presence in serum as assessment tools for joint destruction, which would allow an earlier and more sensitive verification of destructive joint events. We have established that serum markers used in clinical trials and clinical practice are also applicable in experimental arthritis models for the evaluation of joint destruction and of new therapies aimed at preventing destruction We initially demonstrated that serum levels of COMP, BSP, hyaluronan and fibrinogen could be used as markers of cartilage destruction, bone destruction, synovitis and systemic inflammation, respectively in collagen-induced arthritis and oil-induced arthritis. Secondly, we confirmed the usefulness of COMP analysis in the evaluation of the cartilage- saving effects of therapies by comparing serum COMP levels with histological examination of joints. We could demonstrate that corticosteroid treatment, as well as treatment with the novel proinflammatory inhibitor CNI-1493, had cartilage-saving effects. In these studies we could observe a correlation between serum levels of COMP and the degree of cartilage destruction as evaluated by histology. Taken together, these results demonstrate that biological markers for inflammation, synovitis, bone and cartilage destruction can be used in experimental models, both in order to evaluate disease course and severity and in order to evaluate the effects of anti-rheumatic drugs.