COMPARATIVE STUDY OF OSTEOARTHRITIS IN KNEE AND ANKLE

膝关节和踝关节骨关节炎的比较研究

• 批准号: 6332454
• 负责人: KLAUS E KUETTNER
• 金额: $ 27.63万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-15 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6332454
• 关键词: ankle; articular cartilage; biochemistry; biomechanics; bone density; cartilage metabolism; chondrocytes; cytokine receptors; extracellular matrix; extracellular matrix proteins; gene expression; human tissue; in situ hybridization; interleukin 1; knee; mucopolysaccharides; musculoskeletal regeneration; osteoarthritis; photon absorptiometry; polymerase chain reaction; proteoglycan; tomography; tumor necrosis factor alpha

The prevalence of symptomatic osteoarthritis (OA) is higher in some joints, e.g. the knee, than in others, e.g. the ankle. The goal of this project is to compare normal articular cartilage and chondrocytes from these two joints of the same human donor obtained through the Regional Organ Bank of Illinois. Even though the structure/function relationship of these two joints may explain the different prevalence of OA in the knee and ankle, our preliminary data shows that there are significant biochemical differences between the two cartilages. The ankle chondrocytes are less responsive to catabolic mediators that may be due to decreased number of receptors. Compositional analyses show a higher collagen and proteoglycan content with lower water content; thus, the matrix components are more highly concentrated in the ankle cartilage. This is consistent with our biomechanical data showing that ankle chondrocytes form a matrix that is dynamically stiffer with lower hydraulic permeability. Ankle chondrocytes also had decreased gene expression of some matrix metalloproteinases. These data suggest that there are significant differences between normal knee and ankle cartilages that may make the ankle more resistant to degradation and provide protection that may make the ankle more resistant to degradation and provide protection from the progressive destructive changes in OA. Additional protection for the cartilage may be provided by a less responsive underlying bone since analyses of the subchondral bone in the ankles show no increase in bone density with severely damaged cartilage has been reported for the knee. Our hypothesis that the rarity of OA in the ankle joint may be due to the fact that its cartilage is more resistant than knee cartilage to progressive degeneration as a result of 1) decreased responsiveness to catabolic factors, 2) the initiation of repair following and/or 3) biochemical composition, gene expression and biomechanical properties of the cartilage as well as the underlying bone. Our proposed comparative studies not only between the cartilage derived from the different joints but also their degree of damage via biochemical, metabolic, biomechanical modifications will lead to a better understanding of the differences between the two joints. These data may ultimately be useful in the treatment of the OA patient by providing insight into those mechanisms involved in progressive degenerative changes leading to OA in one joint but not the other.

有症状性骨关节炎（OA）的患病率更高 关节，例如膝盖，比其他膝盖，例如脚踝。目标的目标 项目是要比较正常的关节软骨和软骨细胞 通过区域获得的同一人类捐助者的这两个关节 伊利诺伊州的器官银行。即使结构/功能关系 这两个关节可以解释膝盖中OA的不同患病率 和脚踝，我们的初步数据表明有重要的 两个软骨之间的生化差异。脚踝软骨细胞 对可能由于减少而导致的分解代谢介质的反应较低 受体数量。组成分析显示较高的胶原蛋白和 蛋白聚糖含量较低；因此，矩阵组件 在脚踝软骨中更加集中。这是一致的 借助我们的生物力学数据，表明脚踝软骨细胞形成矩阵 这在较低的液压渗透性上动态僵硬。踝 软骨细胞也降低了一些基质的基因表达 金属蛋白酶。这些数据表明有重要的 正常膝盖和踝部软骨之间的差异可能使 踝关节对降解的抵抗力更具，并提供可能使得 脚踝对降解的耐药性更大，并提供保护 OA的逐渐破坏性变化。对 软骨可以通过响应较低的潜在骨骼提供，因为 对脚踝的软骨下骨的分析显示骨骼没有增加 据报道，膝盖已有严重破坏的软骨密度。 我们的假设是，脚踝关节中OA的稀有性可能是由于 事实，其软骨比膝盖软骨更具抵抗力 1）逐渐变性的响应能力降低 分解代谢因素，2）启动维修和/或3） 生化组成，基因表达和生物力学特性 软骨以及下面的骨骼。我们提出的比较 不仅在不同关节衍生的软骨之间进行研究 但也通过生化，代谢，生物力学的损害程度 修改将使人们更好地理解差异 在两个关节之间。这些数据最终可能在 通过洞悉这些机制来治疗OA患者 参与进行性退行性变化，导致一个关节中的OA 但不是另一个。