Establishment of Animal Model and the effect of hyaluronan administration for the cultured chondrocytes transplantation

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Although we planned the experiment of chodrocytes using sheep, it was immediately found that stable supply of sheep was very hard. Then, we changed the plan into using dogs. But, in dogs, harvest of chondrocyte via arthroscopy was almost impossible, due to the size of the joint. So, we changed the plan again into the effects of hyaluronan on the dog osteoarthritis (OA).In the first year, using the dog OA model, the effects of hyaluronan on OA progress were examined. Dogs, whose anterior cruciate ligament were transected, were administered the following 3 agents for 3 weeks after surgery; nothing (Control), hyaluronan intra articular (HA-ia), and hyaluronan iv (HA-iv). Biochemical and morphological examination were performed.Morphologically, the change of the cartilage in HA-iv was significantly small compared to Control. The change in HA-ia was more slight than Controll, but it was not significant. And the chondrocalcin concentration of synovial fluids was significantly highher in HA-iv and HA-ia than Control. These findings indicated that the hyaluronan administration both intra-articular and intarvenous were effective as the treatment for OA in dogs.In the second year, the study was designed to investigate chondrocyte apoptosis in dogs induced OA with anterior cruciate ligament, and to evaluate effects of intraarticular and intravenous injection of HA on the apoptosis of OA model.After anterior cruciate ligament transection, the proportion of apoptosis in chondrocytes was significantly increased. Both intraarticular and intravenous administration of HA were effective to decrease chondrocyte apoptosis.In coclusion, it was considered that HA administration is effective for the OA of dogs through suppression of apoptosis.