Blood-induced joint-damage: Longterm effects in vitro and in vivo

Objective. We previously showed that 4-day in vitro exposure of human cartilage to blood, as well as a single experimental joint bleeding in dogs, resulted in a disturbed cartilage matrix turnover lasting at least 2 weeks. We now evaluate the longterm outcome of the adverse in vitro and in vivo effects of blood on cartilage matrix turnover. Methods. Human and canine articular cartilage tissue was cultured in the presence of homologous whole blood during 4 days. The in vitro cartilage matrix turnover was analyzed directly after blood exposure or following culture for additional periods of 2, 5, and 10 weeks in the absence of blood. The in vivo longterm effects were determined by injecting autologous blood into the right knee of 12 Beagle dogs. Six dogs were killed shortly after blood injections: the 6 remaining dogs were killed 10 weeks later. Cartilage matrix turnover and the cartilage destructive properties of the synovial tissue were analyzed. Results. Short term (4 days) in vitro exposure of human or canine cartilage to whole blood inhibited proteoglycan synthesis by more than 98% (day 4), an inhibition which lasted until week 10 (70 and 75% inhibition, respectively). Also the in vivo short term exposure of cartilage to blood induced the adverse changes in cartilage proteoglycan turnover seen shortly after exposure. However, in vivo 10 weeks after the last injection, normalization of cartilage matrix turnover was observed. Synovial inflammation was absent and no destructive activity was found. Conclusion. These data show a discrepancy between the in vitro and in vivo longterm effects of blood on cartilage. A possible explanation for the in vivo recovery after experimental joint bleeding in dogs could be that the observed changes in cartilage only predispose to acute damage but that additional (e.g., mechanical) factors are needed to induce permanent joint damage.