Search

Objective: To evaluate the anabolic activity of osteoarthritic chondrocytes in situ by investigating the messenger RNA (mRNA) expression of 3 major cartilage components, type II collagen, aggrecan, and link protein:, Methods: In situ hybridization experiments and histochemical analysis for proteoglycan content were performed on parallel sections of normal and osteoarthritic (OA) cartilage specimens., Results: Most chondrocytes in the deeper.zones of OA cartilage showed an increase in mRNA expression, in particular, of type II collagen and to a lesser extent, aggrecan, compared with normal specimens. However, chondrocytes of the upper zone were largely negative for aggrecan or type II collagen mRNA. The expression of link protein mRNA was low in normal and OA specimens., Conclusion: These observations suggest that suppression of the anabolic activity of chondrocytes in the upper zones contributes to the metabolic imbalance observed in OA cartilage. Stimulation of matrix anabolism in superficial chondrocytes might be a suitable target for therapeutic intervention.

Increased levels of inflammatory cytokines such as II-1 and TNF-alpha are described in rheumatoid and osteoarthritic synovial fluid. These mediators are also very well established anti-anabolic modulators of chondrocyte synthetic activity in vitro. Our study aimed to investigate, whether chondrocytes in rheumatoid and osteoarthritic cartilage in situ show reaction pattern compatible with the putative effects of these modulatory agents. Immunohistochemical analysis using type II collagen specific antibodies showed considerable loss of staining in many sites of osteoarthritic and rheumatoid articular cartilage. mRNA analysis showed besides an overall activation of synthetic activity in rheumatoid and osteoarthritic cartilage, a decreased expression of cartilage matrix proteins in the upper zone. The cease of the anabolic activity of rheumatoid and osteoarthritic chondrocytes and the increased catabolism of matrix components contributes to the anabolic-catabolic imbalance in rheumatoid and osteoarthritic cartilage and is suggestive to be a crucial event in the progress of the disease. It correlates well to the putative anti-anabolic effect of inflammatory cytokines such as II-1 and TNF-alpha and could indicate a potential role of these mediators in rheumatoid and osteoarthritic cartilage destruction.