Increased apoptosis in human osteoarthritic cartilage corresponds to reduced cell density and expression of caspase-3

Objective. Chondrocyte apoptosis has been described in both human and experimentally induced osteoarthritis (OA), but its importance in the etiopatho-genesis of OA is uncertain. The aims of this study were to determine the rate of chondrocyte apoptosis using different methods, and to investigate the relationship between this process and cartilage cellularity, expression of proapoptotic molecules, and expression of antiapoptotic molecules in articular cartilage obtained from patients with OA and from nonarthritic controls. Methods. We examined the extent of apoptosis in OA and nonarthritic control cartilage using expression of caspase-3, an enzyme that mediates the final stage of cell death by apoptosis, as well as the TUNEL method. We used immunohistochemistry to analyze the expression of a panel of proapoptotic and antiapoptotic molecules that regulate apoptosis in articular cartilage, in order to determine whether the rate of apoptosis is associated with the expression of these molecules. Results. The median (range) percentage of TUNEL-positive chondrocytes in knee OA cartilage (n = 10 specimens), hip OA cartilage (n = 9), and control cartilage (n = 7) was 3.11 (1.67-3.67), 1.86 (1.22-2.89), and 0.39 (0.00-1.78), respectively. When all cartilage samples were pooled, apoptosis showed a strong inverse correlation with cellularity (r = -0.74, P < 0.0001). The percentage (range) of cells expressing caspase-3 in the 3 groups was 15.70 (7.40-20.50), 15.77 (7.42-20.5), and 7.40 (5.90-8.00), respectively. One-way analysis of variance showed that the differences between groups for both TUNEL-positive cells and expression of caspase-3 were statistically significant (P < 0.0001). There was a significant positive correlation between TUNEL-positive cells and expression of caspase-3 (r 0.654, P < 0.01). Conclusion. The data suggest that apoptosis is increased, on average, 2-4-fold in OA cartilage. Considering that OA develops over many years, such an increase in the rate of apoptosis in the articular cartilage could play an important role in the disease process.