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.

尽管我们计划使用绵羊进行鸡蛋细胞的实验，但立即发现绵羊的供应非常困难。然后，我们将计划更改为使用狗。但是，在狗中，由于关节的大小，通过关节镜检查收获软骨细胞几乎是不可能的。因此，我们再次将计划更改为透明质酸对狗骨关节炎（OA）的影响。第一年，使用狗OA模型，研究了透明质酸对OA进度的影响。犬的前交叉韧带被横断的狗在手术后3周内服用3周的狗。什么都没有（对照），透明质酸关节内（HA-IA）和透明质酸IV（HA-IV）。进行了生化和形态检查。从形态学上，与对照相比，HA-IV中软骨的变化显着小。 HA-IA的变化比控制更小，但并不重要。在HA-IV和HA-IA中，滑动流体的软骨素浓度比对照明显高。 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横向，软骨细胞中细胞凋亡的比例显着增加。关节内和静脉内HA的给药均有效降低软骨细胞凋亡。在稳定性中，人们认为HA给药可通过抑制凋亡对狗的OA有效。