PROTEOGLYCANS/MATRIX ASSEMBLY IN REGENERATING CARTILAGE

软骨再生中的蛋白聚糖/基质组装

• 批准号: 6657258
• 负责人: Theodore Richard Oegema
• 金额: $ 27.88万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-02-25 至 2004-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6657258
• 关键词: biological models; cartilage metabolism; chondrocytes; chondroitin sulfates; collagen; decorin; extracellular matrix; laboratory rabbit; osmotic pressure; polymers; protein biosynthesis; protein structure function; proteoglycan; tissue /cell culture

DESCRIPTION: (adapted from applicant's abstract) Proteoglycans (PG) are recognized as important constituents of the mechanical properties of cartilage. However, the possibility that PG influence matrix quality by regulating cell functions has not been examined in detail and mechanisms of matrix assembly have not been examined. These processes are important for cartilage engineering and the proposal will establish the effect of PG on the assembly of neocartilage matrix and to use artificial polymers to direct this effort. The applicants have developed a rabbit articular chondrocyte culture model that allows biochemical, metabolic, morphological and biomechanical analyses. With this model it was demonstrated that polyethylene glycol as a surrogate for aggrecan to control osmotic pressure and exclude volumes increased PG synthesis and matrix content. The proposed studies will (1) test the hypothesis that the effect of exogenous aggrecan on matrix synthesis during the critical phase of matrix accumulation by cultured chondrocytes is due only to the osmotic properties of aggrecan; (2) determine how the structure of aggrecan or aggrecan substitutes promote assembly; (3) determine whether aggrecan promotes matrix assembly during the critical transitional phase by providing physical-chemical properties and not structural properties; (4) examine whether in the presence of adequate aggrecan the diameter of the collagen fibril will control the effectiveness of the collagen network in retaining aggrecan.

描述：（改编自申请人的摘要）蛋白聚糖（PG）是 被认为是软骨机械性能的重要组成部分。 然而，PG通过调节细胞而影响基质质量的可能性 功能尚未详细检查，矩阵组装的机制 还没有被检查过。这些过程对于软骨工程非常重要 该提案将确定PG对组装的影响， 新软骨基质，并使用人工聚合物来指导这一努力。的 申请人开发了一种兔关节软骨细胞培养模型， 允许进行生物化学、代谢、形态学和生物力学分析。与 该模型表明，聚乙二醇作为 聚集蛋白聚糖控制渗透压和排除体积增加PG合成 和基质含量。拟议的研究将（1）检验假设， 外源性聚集蛋白聚糖对基质合成的影响 培养的软骨细胞的基质积累仅仅是由于渗透压 （2）确定聚集蛋白聚糖或聚集蛋白聚糖的结构如何 替代物促进组装;（3）确定聚集蛋白聚糖是否促进基质 在关键的过渡阶段，通过提供物理化学 （4）检查是否有结构性的特征; 足够的聚集蛋白聚糖的胶原纤维的直径将控制 胶原网络在保留聚集蛋白聚糖中的有效性。