Study on the treatment of osteoarthritis using sheep model

绵羊模型治疗骨关节炎的研究

• 批准号: 10839005
• 负责人: MOCHIZUKI Manabu
• 金额: $ 2.18万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10839005/
• 关键词: OSTEOARTHRITIS; CRANIAL CRUCIATE LIGAMENT; SHEEP; CARTILAGE; HYALURONAN; MATRIX METALLOPROTEINASE; 変性性関節症; 前十字靱帯; 骨関節症

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.

在第一年，我们试图使用绵羊创建骨关节炎（OA）模型。健康绵羊的左窒息关节中的颅交叉韧带进行了手术转移。每4周收集滑液进行生化检查。手术后十二和二十四个星期，对动物进行了安乐死，并将窒息的关节腔化进行宏观和组织学检查。从声学上讲，关节的软骨被退化并破坏，并在手术后12周发生骨theo骨。这些形态学变化并未从12到24周发展。生化检查并未揭示韧带的韧带和对照组之间的任何重大变化。这些发现表明，颅相当韧带的交易诱导了绵羊膝关节中的OA样性的OA样变化。检查了OA的进度。绵羊的颅韧带转移了，在手术后11周内服用了以下4个特工。盐水IV（NaCl），透明质酸关节内（HA-IA），透明质酸IV（HA-IV）和基质金属蛋白酶抑制剂IV（MMPI）。进行了生化和形态学检查。在药物之间的生化结果中没有明显的尊重。从形态上讲，与NaCl相比，HA-IV中软骨的变化显着很小。 HA-IA的变化更多。比NaCl轻微，但这并不重要。 MMPI中的软骨与NACL的程度相同。这些发现表明，透明质酸给药的关节内和静脉注射均有效作为OA治疗。