AGE DEPENDENT EXPRESSION OF CARTILAGE PROTEOGLYCANS

软骨蛋白聚糖的年龄依赖性表达

• 批准号: 2705989
• 负责人: GABRIELLA CS-SZABO
• 金额: $ 6.88万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 2000-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2705989
• 关键词: aging; biochemistry; cartilage; chondrocytes; chondroitin sulfates; decorin; gene expression; histopathology; human old age (65+); human tissue; messenger RNA; osteoarthritis; phenotype; polymerase chain reaction; protein degradation; protein isoforms; proteoglycan; radioimmunoassay

Morphological abnormalities (usually surface erosion) of the articular cartilage can be detected in approximately 70 percent of the human population over age 65. Essentially everyone with these degenerative abnormalities of the articular cartilage is listed under one of the most frequent age-associated disease, osteoarthritis (OA). Osteoarthritis, however, is a complex joint disease and, while it is characteristic, cartilage erosion is only one concomitant symptom of the disease process. We hypothesize that the degradation of articular cartilage is essentially an age-associated physiological process of heavily-used joints, and OA is the result of pathological events accompanies by change of chondrocyte phenotype. Now, we propose comparative studies of biochemical and histopathological parameters in an age-range of 40-70-year old population having no clinical records of joint abnormalities. To confirm our hypothesis, these results will be correlated with our previous observations of clinically diagnosed OA groups. We will measure four biochemical parameters (re-expression of a fetal-type epitope of aggrecan, substitution of fibromodulin with keratin sulfate, appearance of splice variants of decorin, and increased expression of small proteoglycans) which appear to be obligatory components of chondrocyte phenotype in OA, but not in normal aging cartilage. These normal versus altered chondrocyte phenotypes will then be correlated with the morphological appearance of the articular cartilage. We propose two specific aims: (1) to follow biochemical changes of cartilage components specifically altered in OA but not expected in normal aging tissue, and (2) to correlate these biochemical samples of patients with clinically end-stage OA. These experiments will explore molecular changes during the aging of cartilage and may segregate normal aging events from those of early OA changes.

关节形态异常（通常是表面侵蚀） 大约 70% 的人体中可以检测到软骨 65 岁以上的人口。基本上每个人都患有这些退行性疾病 关节软骨异常被列为最常见的异常之一 常见的与年龄相关的疾病，骨关节炎（OA）。骨关节炎， 然而，这是一种复杂的关节疾病，虽然具有特征性， 软骨侵蚀只是疾病过程的伴随症状之一。 我们假设关节软骨的退化本质上是 频繁使用关节的与年龄相关的生理过程，OA 是 病理事件的结果伴随着软骨细胞的变化 表型。 现在，我们提出生化和组织病理学的比较研究 40-70岁人群年龄范围内无临床症状的参数 关节异常的记录。为了证实我们的假设，这些结果 将与我们之前对临床诊断的观察结果相关 OA 组。我们将测量四个生化参数（重新表达 聚集蛋白聚糖的胎儿型表位，用纤维调节蛋白替代 硫酸角蛋白、核心蛋白聚糖剪接变体的出现以及增加 小蛋白多糖的表达）这似乎是强制性的 OA 中软骨细胞表型的组成部分，但正常衰老中则不然 软骨。这些正常与改变的软骨细胞表型将被 与关节软骨的形态外观相关。 我们提出两个具体目标：（1）跟踪生物化学变化 软骨成分在 OA 中发生特别改变，但在正常情况下不会发生改变 老化组织，以及 (2) 将患者的这些生化样本关联起来 临床上患有终末期 OA。这些实验将探索分子 软骨老化过程中的变化，可能会隔离正常老化 早期 OA 变化的事件。