Study on the treatment of osteoarthritis using sheep model

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In the first year, we tried to create the osteoarthritis (OA) model using sheep. Cranial cruciate ligaments in the left stifle joint of health sheep were surgically transected. Every 4 weeks, the synovial fluid were collected for biochemical examination. Twelve and twenty-four weeks after surgery, the animals were euthanized and the stifle joints were colelected for macroscopic and histological examination.Morphologically, the cartilage of the joints were degenerated and destructed, and the osteophytosis occurred at 12 weeks after surgery. Those morphological changes did not developed from 12 to 24 weeks. Biochemical examination did not reveal any significant changes between ligament transected animals and control ones.These findings indicated that transaction of the cranial cruciate ligament induced the OA-like-changes of the cartilage in the knee of sheep by 12 weeks, and that this can be a suitable OA animal model.In the second year, using the sheep OA model, the effects of hyaluronan and matrix metalloproteinase inhibitor on OA progress were examined. Sheep, whose cranial cruciate ligament were transected, were administered the following 4 agents for 11 weeks after surgery ; saline iv (NaCl), hyaluronan intra articular (HA-ia), hyaluronan iv (HA-iv) and matrix metalloproteinase inhibitor iv (MMPI). Biochemical and morphological examination were performed.No significant deference were found in the biochemical results between the agents. Morphologically, the change of the cartilage in HA-iv was significantly small compared to NaCl. The change in HA-ia was more. slight than NaCl, but it was not significant. The cartilage in MMPI was destroyed to the same degree as NaCl.These findings indicated that the hyaluronan administration both intra-articular and intravenous were effective as the treatment for OA.