LIPIDS IN THE PATHOGENESIS OF OSTEOARTHROSIS

透明软骨细胞中也含有脂质 但它们对软骨细胞功能的重要性 以及未知的新陈代谢。 正常情况下， 尽管在健康组织中沉积物的类似增加 也与疾病状态和创伤有关。 软骨细胞很容易并且可能选择性地摄取脂质， that levels水平and trauma创伤. 软骨细胞很容易 选择性地摄取脂质， 摄入量可能会影响软骨中的脂质分布， 维持细胞脂质恒定的控制系统。 在关节病的不稳定模型中观察到脂肪关节病， 与早熟关节病相关的遗传性疾病， 关节软骨受到创伤性损伤 这项建议解决了脂质在正常人中的作用问题。 软骨，探讨是否与年龄相关的脂质积累， 促进/引发软骨细胞代谢的畸变， 可能导致组织退化 第二种方法是检查 如果载脂细胞能够维持稳态， 暴露于机械刺激。 一系列的两个主要实验进行了说明。 在体外，我们将 研究脂质中特定脂肪酸谱的变化 差异性地影响软骨细胞的代谢， 蛋白聚糖和胶原的生物合成，以及在体内，使用 饮食控制细胞脂质含量。 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。 的假设 待测试的是特定的脂肪酸（即，20：4）影响力 软骨代谢时，在过量和脂质- 负载的细胞失去其承受机械力的能力。 第二，高脂血症状态诱导软骨异常 如果软骨细胞的脂质代谢包括 必需脂肪酸花生四烯酸或亚油酸。 是 私家侦探的意图启动有关机制的试点研究， 脂质积累改变正常的软骨生理学。 这些 包括对膜流动性、能量储存/利用 和与大分子的物理相互作用。

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.