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

动物模型的建立及透明质酸注射对培养软骨细胞移植的影响

• 批准号: 14560261
• 负责人: MOCHIZUKI Manabu
• 金额: $ 2.3万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14560261/
• 关键词: dog; cartilage; osteoarthritis; apoptosis; hyaluronan

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.

虽然我们计划使用绵羊进行软骨细胞实验，但立即发现绵羊的稳定供应非常困难。然后，我们改变了计划，使用狗。但是，在狗中，由于关节的大小，通过关节镜手术采集软骨细胞几乎是不可能的。因此，我们将计划再次改为透明质酸对犬骨关节炎（OA）的影响，在第一年，使用犬OA模型，检查透明质酸对OA进展的影响。在手术后3周内，对前交叉韧带横断的犬给予以下3种药物：无药物（对照）、关节内透明质酸（HA-ia）和静脉注射透明质酸（HA-iv）。形态学观察表明，HA-iv组软骨的形态学改变明显小于对照组。HA-ia的变化比对照组轻微，但不显著。关节液中软骨钙素浓度HA-1a组和HA-iv组均显著高于对照组。第二年，本研究采用犬前交叉韧带关节炎模型，观察关节内注射和静脉注射透明质酸对关节炎软骨细胞凋亡的影响，并观察关节内注射和静脉注射透明质酸对关节炎软骨细胞凋亡的影响。软骨细胞凋亡比例明显增加。关节腔内和静脉注射HA均能有效地减少软骨细胞凋亡，提示HA治疗OA是通过抑制软骨细胞凋亡实现的。