LIPIDS IN THE PATHOGENESIS OF OSTEOARTHROSIS

脂质在骨关节炎发病机制中的作用

• 批准号: 3159415
• 负责人: LOUIS LIPPIELLO
• 金额: $ 10.46万
• 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/3159415
• 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.

脂质在透明软骨细胞中也是恒定的内含物