PHYSIOLOGIC MODULATION OF ARTICULAR CARTILAGE

关节软骨的生理调节

• 批准号: 3152977
• 负责人: KENNETH D BRANDT
• 金额: $ 8.02万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-04-01 至 1986-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3152977
• 关键词: articular cartilage; carbohydrate biosynthesis; cartilage metabolism; chondroitin sulfates; connective tissue metabolism; exercise; extracellular matrix; femur; gel filtration chromatography; histology; joints; keratan sulfate; mucopolysaccharides; osteoarthritis; proteoglycan; radiotracer; skeletal stress; uronate

The proposed study examines the ability of normal articular cartilage to alter its metabolism, and the composition of its matrix, in response to local changes in joint loading. A non-invasive, physiologic exercise protocol has been developed which has been shown to alter loading in the canine humeral head. In this model, dogs are walked daily in an exercise carousel, with a series of low steps placed in the exercise path. Kinematic analyses have shown that dismounting the steps induces compressive loading in the caudal-central region of the humeral head, which is normally unloaded. Notably, it is also the site in which osteoarthritis of the shoulder develops in aging dogs. Histochemical studies of cartilage from dogs placed on the step-walking protocol for 6 months suggest that an increase in chondroitin sulfate content occurs in the lesion-prone caudal-central region, while cartilage from the dorsal plateau remains histochemically normal. In the proposed study the apparent modulation in glycosaminoglycan content of cartilage resulting from this exercise regimen will be studied chronologically, and and attempt will be made to confirm the histochemical findings by biochemical and metabolic studies. Six control dogs will be permitted only limited exercise. Eighteen dogs will be exercised by walking over a flat path for 1, 3 or 6 months (6 dogs/time period), while a third group of 18 dogs will be similarly exercised over a path containing low steps for 1, 3 or 6 months. At sacrifice, cartilage from the dorsal plateau and caudal-central regions of each humeral head will be obtained for histochemical studies, and for analyses of water, uronic acid and collagen contents, and glucosamine:galactosamine molar ratios (to measure ratios of keratan sulfate: chonodroitin sulfate). In addition, the influence of the altered load pattern on glycosaminoglycan synthesis and degradation, and on the hydrodynamic size of newly-synthesized and total tissue proteoglycan subunits and aggregates will be studied. The data should help elucidate the relationships which exist in this model between alterations in load and chondrocyte metabolism, and may serve as a basis for understanding the role of mechanical factors in maintaining the integrity of articular cartilage, or in facilitating its breakdown.

这项拟议中的研究检查了正常关节软骨 改变其代谢和基质的组成，以响应 关节载荷的局部变化。 一种非侵入性的生理运动 已经开发了一种协议，该协议已被证明可以改变 犬齿肱骨头 在这个模型中，狗每天都在锻炼中散步， 旋转木马，与一系列低步骤放置在行使路径。 运动学分析表明， 肱骨头尾侧中心区域的压缩载荷， 通常是无负荷的。 值得注意的是，它也是骨关节炎 肩关节在年老的狗身上发育。 软骨组织化学研究 从狗放置在步进步行协议6个月表明， 硫酸软骨素含量增加发生在病变倾向 尾部中央区域，而背侧平台的软骨保留下来 组织化学正常。 在拟议的研究中，糖胺聚糖含量的明显调节 将研究这种锻炼方案产生的软骨 按时间顺序，并试图确认组织化学 生物化学和代谢研究的结果。 六只对照犬将 只允许有限的锻炼。 18只狗将被训练 在平坦的路径上行走1、3或6个月（6只狗/时间段），而 第三组十八只狗将同样地在一条小路上训练， 1、3或6个月的低台阶。 在处死时，背侧的软骨 将获得每个肱骨头的平台和尾侧中心区域 用于组织化学研究，并用于分析水、糖醛酸和 胶原含量和葡糖胺：半乳糖胺摩尔比（以测量 硫酸角质素：硫酸软骨素的比例）。 此外该 改变的负荷模式对糖胺聚糖合成的影响， 降解，以及对新合成的和总的 将研究组织蛋白聚糖亚单位和聚集体。 数据 应该有助于阐明存在于这个模型中的关系， 负荷和软骨细胞代谢的改变，并可作为基础 为了理解机械因素在维持 关节软骨的完整性，或促进其分解。