LIPIDS IN THE PATHOGENESIS OF OSTEOARTHROSIS

脂质在骨关节炎发病机制中的作用

• 批准号: 3159419
• 负责人: LOUIS LIPPIELLO
• 金额: $ 8.68万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3159419
• 关键词: aging; arachidonate; bioenergetics; cartilage metabolism; chondrocytes; collagen; cow; dietary excess; dietary lipid; hamsters; hyperlipoproteinemia; inborn metabolism disorder; laboratory rabbit; linoleate; mechanical stress; membrane lipids; membrane structure; osteoarthritis; parathyroid hormones; proteoglycan; unsaturated fats

Lipids are constant inclusions in chondrocytes of hyaline as well as other cartilages but their significance to chondrocyte function and metabolism in unknown. Lipids accumulate during normal aging in healthy tissue although similar increases in deposits have also been associated with disease states and trauma. Chondrocytes readily and perhaps selectively take up lipids so that levels and trauma. Chondrocytes readily and perhaps selectively take up lipids so that levels and types of dietary lipid intake may influence lipid profiles in cartilage in spite of cellular control systems operating to maintain cell lipid constancy. Lipoarthrosis has been observed in instability models of arthrosis, in an inherited disease associated with precocious arthrosis and following traumatic insults to articular cartilage. This proposal addresses the question of the role of lipid in normal cartilage by exploring whether age-related lipid accumulation promotes/initiates aberrations in chondrocyte metabolism which may lead to tissue degeneration. A second approach is to examine if lipid-laden cells can maintain a homeostatic state upon exposure to mechanical stimuli. A series of two major experiments are described. In vitro we will study whether variations in specific fatty acid profiles of lipids differentially affect chondrocyte metabolism as indicated by biosynthesis of proteoglycans and collagen, and in vivo, using dietary manipulation of cell lipid content. The latter study will explore the effects of hyperlipoproteinemia (hypercholesterolemia) on cartilage metabolism. The hypothesis to be tested is that specific fatty acids (i.e., 20:4) influence cartilage metabolism when accumlated in excess and that lipid- laden cells lose their capacity to withstand mechanical forces. Second, a state of hyperlipidemia induces aberrant cartilage metabolism if lipid accumalation by chondrocytes includes the essential fatty acids arachidonic acid or linoleic acid. It is the intent of the P.I. to initiate pilot studies on mechanisms whereby lipid accumulation alters normal cartilage physiology. These include effects on membrane fluidity, energy storage/utilization and physical interaction with macromolecules.

脂类也是透明软骨细胞中的恒定包裹体。 但它们对软骨细胞功能的意义 以及未知的新陈代谢。脂类在正常情况下积聚 健康组织中的衰老，尽管沉积的类似增加 也与疾病状态和创伤有关。 软骨细胞很容易而且可能有选择性地摄取脂质 这样的水平和创伤。软骨细胞很容易而且可能 有选择地摄取脂肪，以便饮食中脂肪的水平和类型 摄入可能影响软骨中的脂类，而不是细胞 维持细胞脂质恒定的控制系统。 在关节不稳定模型中观察到了脂肪关节， 在一种与性早熟有关的遗传病中 在关节软骨受到创伤性侮辱之后。 这项建议解决了脂质在正常情况下的作用问题 通过探索软骨中与年龄相关的脂质堆积 促进/启动软骨细胞代谢的异常 可能会导致组织退化。第二种方法是检查 如果载脂细胞能维持体内平衡状态 暴露在机械刺激下。 描述了一系列两个主要的实验。在体外，我们将 研究脂类特定脂肪酸组成的变化是否 差异性影响软骨细胞新陈代谢 蛋白多糖和胶原蛋白的生物合成，以及在体内，使用 对细胞脂肪含量的饮食控制。后一项研究将 探讨高脂蛋白血症的影响 (高胆固醇血症)对软骨代谢的影响。假说 要测试的是特定的脂肪酸(即20：4)影响 当软骨代谢过量时，脂肪- 负载细胞失去了承受机械力的能力。 第二，高脂血症会导致软骨畸形。 如果软骨细胞的脂肪堆积包括代谢 必需脂肪酸花生四烯酸或亚油酸。它是 私人投资局打算启动关于以下机制的试验性研究 脂肪堆积改变了正常的软骨生理。这些 包括对膜流动性、能量存储/利用 以及与大分子的物理相互作用。