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: 6295696
• 负责人: KLAUS E KUETTNER
• 金额: $ 17.02万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-06 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6295696
• 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.

有症状的骨关节炎(OA)在某些地区的患病率更高 关节，如膝盖，比其他地方，如脚踝。这样做的目的是 项目是比较正常的关节软骨和来自 同一人体供体的这两个关节是通过区域组织获得的 伊利诺伊州器官银行。即使分子的结构/功能关系 这两个关节可能解释了膝关节骨关节炎发病率不同的原因。 和脚踝，我们的初步数据显示，有显著的 两个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差，这可能是由于 受体的数量。成分分析显示更高的胶原蛋白和 蛋白质多聚糖含量较低；因此，基质成分 更高度集中在脚踝软骨中。这是一致的 我们的生物力学数据显示脚踝软骨细胞形成基质 这是动态刚性较低的水力渗透性。脚踝 软骨细胞中某些基质的基因表达也降低。 金属蛋白酶。这些数据表明，有显著的 正常膝关节和踝关节软骨之间的差异可能使 脚踝更耐退化，并提供保护，可能会使 脚踝更能抵抗退化，并提供保护免受 办公自动化中的渐进式破坏性变化。提供额外的保护 软骨可能由反应较弱的下层骨提供，因为 对踝关节软骨下骨的分析显示骨量没有增加。 据报道，膝关节的密度和严重的软骨损伤。 我们的假设是，踝关节骨性关节炎的罕见可能是由于 它的软骨比膝关节软骨更能抵抗 由于1)反应性降低而导致的进行性退化 分解代谢因素，2)修复的启动和/或3) 生物化学组成、基因表达及生物力学特性 软骨和下面的骨头。我们建议的比较 不仅研究了软骨来源的不同关节 以及它们在生化、代谢、生物力学方面的损伤程度 修改将导致对差异的更好理解 在两个关节之间。这些数据最终可能在 通过对这些机制的深入了解来治疗骨性关节炎患者 参与进行性退行性改变，导致一个关节的骨性关节炎 但不是另一个。