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: 6434892
• 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: 2001
• 资助国家: 美国
• 起止时间: 2001-01-01 至 2001-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6434892
• 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.

症状性骨关节炎（OA）的患病率在一些 关节，例如膝盖，比其他关节，例如脚踝。这个目标 该项目是比较正常关节软骨和软骨细胞， 这两个关节来自同一个人类捐赠者， 伊利诺伊州器官银行尽管结构/功能关系 这两个关节可能解释了膝关节OA患病率的不同 和脚踝，我们的初步数据显示， 两种软骨之间的生化差异。踝关节软骨细胞 对分解代谢介质的反应较低，这可能是由于 受体的数量。成分分析显示，胶原蛋白含量较高， 蛋白聚糖含量与较低的水含量;因此，基质组分 集中在脚踝软骨上这是一致 我们的生物力学数据显示踝关节软骨细胞形成了一个基质 其具有更低的水力渗透性的动态刚性。脚踝 软骨细胞也有一些基质的基因表达减少 金属蛋白酶这些数据表明， 正常膝关节和踝关节软骨之间的差异， 脚踝更耐降解，并提供保护， 脚踝更能抵抗降解，并提供保护， OA的进行性破坏性变化。为客户提供额外保护 软骨可以由反应性较低的下层骨提供， 对踝关节软骨下骨的分析表明， 已经报道了膝关节的密度和严重受损的软骨。 我们假设踝关节OA的罕见性可能是由于 事实上，它的软骨比膝盖软骨更能抵抗 进行性变性，由于1）对 分解代谢因素，2）以下修复的启动和/或3） 生物化学成分、基因表达和生物力学性能 软骨和下面的骨头。我们的建议比较 研究不仅在来自不同关节的软骨之间 而且还通过生化、代谢、生物力学 修改将导致更好地理解差异 在两个关节之间。这些数据最终可能会在 通过深入了解这些机制来治疗OA患者 参与导致一个关节OA的进行性退行性变化 而不是另一个。