AGE RELATED DIFFERENCES IN CHONDROCYTE MMP-8

骨关节炎(OA)是一种主要影响关节衰弱的疾病 老年人。有症状的骨性关节炎在膝关节中的患病率较高， 而不是脚踝。作为进行性软骨退行性变可见的骨关节炎 在成年后显著增加，重要的是了解更多关于 驱动正常衰老的机制。拟议研究的一个优势 使用来自人类器官捐赠者的踝关节软骨是 记录很少发生骨性关节炎的关节的软骨变化。瘦的 踝关节软骨可作为研究正常衰老的理想模型 对导致疾病的变化没有影响的过程。一个 这项研究对数据的重大发现是建立了一个 关节分级系统，其中软骨已被取走，以便 软骨可以被识别为正常或受损，区分 正常(非病理性进行性)衰老过程和病理性衰老 软骨进行性退行性变。从我们的研究中剔除 有骨性关节炎迹象的软骨，我们打算只鉴定那些生化的 和/或与年龄有关的分子生物学差异。这个 这个项目的独特之处在于我们可以不受限制地接触人类 组织。所有接受测试的脚踝软骨都来自人类器官捐赠者。 在24小时内通过伊利诺伊州地区器官银行收取 死亡。在拟议的研究中，我们选择调查 人体踝关节衰老过程中的基质金属蛋白酶-8 4个年龄组的软骨：1)10岁以下：2)20~40岁； 3)40-60岁；4)60岁及以上。我们选择了这个 蛋白酶，因为它对胶原蛋白和 聚集素是细胞外基质的主要成分。我们的 初步数据显示，在相对年轻的成年踝关节 软骨基质金属蛋白酶-8的表达为阴性或几乎检测不到。 然而，这种蛋白酶在骨性关节炎软骨中高度上调。 老年病人。我们假设踝关节软骨的正常老化 基质金属蛋白酶-8的表达和活性正在发生一些调节，但确实 不会加速蛋白聚糖和胶原蛋白的分解代谢。整体而言 拟议研究的目标是1)定义与年龄相关的变化 软骨细胞基质金属蛋白酶-8和2)的特异性变化 如果暴露在空气中会加剧软骨退变，则会随着年龄的增长而发生 分解代谢介体，白介素1，在有效改变的浓度 基质稳态代谢。一旦参与了基质金属蛋白酶-8的正常 更好地了解软骨的老化，这里介绍的方法 可能对确定基质金属蛋白酶-8在疾病相关疾病中的作用最有帮助 流程(长期目标)。

Osteoarthritis (OA) is a debilitating joint disease affect primarily the elderly. The prevalence of symptomatic OA is higher in the knee joint, than in the ankle. As progressive cartilage degeneration seen in OA increased markedly during adult life, it is important to learn more about the mechanisms driving normal aging. An advantage of the proposed study using the ankle cartilage from human organ donor is the opportunity of documenting cartilage changes in a joint that rarely develops OA. Thin ankle cartilage could serve as an ideal model for studying normal aging processes which do not have impact of changes leading to disease. A significant finding of this study to data has been the establishment of a grading system for joints which cartilage has been taken so that the cartilages could be identified as normal or damaged distinguishing between normal (non pathologically progressive) aging process and pathologically progressive degeneration of cartilage. By eliminating from our studies cartilages with signs of OA, we intend to identify only those biochemical and/or molecular biological differences which are age-related. The uniqueness of this project is that we have unlimited access to human tissue. All ankle cartilages to be tested are from human organ donors collected through the Regional Organ Bank of Illinois within 24 hours of death. For the proposed studies we have chosen to investigate the role of one of the matrix metalloproteinase (MMP), MMP-8, in aging of human ankle cartilage from four age groups: 1) under 10 years old; 2) 20-40 years old; 3) 40-60 years old and 4) 60 and over years old. We have selected this proteinase because of its catalytic activity against both collagen and aggrecan, the major components of the extracellular matrix. Our preliminary data indicate that in relatively young adult ankle articular cartilage the expression of MMP-8 mRNA is negative or barely detectable, however this proteinase is highly up-regulated in OA cartilages from elderly patients. We hypothesize that with normal aging of ankle cartilage some modulation of MMP-8 expression and activity is taking place, but does not lead to accelerated catabolism of aggrecan and collagen. The overall goals of the proposed studies are 1) to define age-related changes in chondrocyte MMP-8 and 2) to study specific changes which the proteinase undergoes with age if cartilage degeneration is enhanced by exposure to catabolic mediator, interleukin-1, at concentrations effective in altering matrix steady state metabolism. Once the involvement of MMP-8 in normal aging of cartilage is better understood, the approaches presented here could prove most helpful in defining the role of MMP-8 in disease-related processes (long-term goal).