The Effect of Repeated Intraarticular Bleeding in the Synovium and Articular Cartilage: An Animal Model

Abstract

Purpose: We designed this study to demonstrate the pathophysiology of hemophilic arthropathy (HA) by creating an animal model for determining the effect of repeated intraarticular bleeding in the synovium and articular cartilage. Materials and Methods: 20 normal male New Zealand white rabbits were used for this study. We injected 1 ml of autologous blood from the ear vein of the rabbits into the right knee joint three timeds a week for 18 weeks, and we injected 1 ml of normal saline into the left knee joint three times a week for 18 weeks as a control group. We examined the pathologic changes by microscopy and plain X-ray, and we determined the mRNA expression of proinflammatory cytokines in the synovium of the HA by performing real time RT-PCR at the 11 th week and 18 th week after starting blood-injection. We also examined the GAG and the PGE2 production in cultured chondrocytes that were extracted from the HA knees. Results: At the 11 th week, after blood injection there were no remarkable gross changes in the HA knees and the control knee joints. At the 18 th weeks, the experimental knee joints (HA knees) showed grossly swelling and degenerative changes by X-ray. The infiltration of inflammatory cells and the synovial pro- liferation in the HA knee joints were compared with that in the control knee joints by microscopic examination. The expressions of the mRNA of TNF-alpha, IL-1, MMP-1 and MMP-3 in the HA synovium were increased, as determined by real time RT- PCR, as compared with that in the control knee. In the cultured chondrocytes, the GAG production was decreased and the PGE2 was increased, but the MMP-1 and MMP-3 were not changed, as determined by ELISA. Conclusion: Our results showed that the GAG production of chondrocytes of the HA knees was decreased and there was increased PGE2, so that the cartilage degeneration by intra-articular bleeding was caused by the decreased metabolism of chondrocytes rather than by increased catabolism of the chondrocytes. We suggest that HA was associated with synovitis and cartilage degeneration, but decreased cartilage metabolism was the major mechanism of HA.