PROTEOGLYCANS/MATRIX ASSEMBLY IN REGENERATING CARTILAGE

软骨再生中的蛋白聚糖/基质组装

• 批准号: 6349980
• 负责人: Theodore Richard Oegema
• 金额: $ 26.59万
• 依托单位: UNIVERSITY OF MINNESOTA
• 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 2004-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6349980
• 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可能通过调节细胞影响基质质量。 尚未详细研究矩阵组装的功能和机制 没有经过检查。这些过程对于软骨工程很重要 该提案将确定 PG 对组装的影响 新软骨基质并使用人造聚合物来指导这一努力。这 申请人开发了一种兔关节软骨细胞培养模型， 允许进行生化、代谢、形态学和生物力学分析。和 该模型证明聚乙二醇可以作为 聚集蛋白聚糖控制渗透压并排除增加的 PG 合成量 和基质含量。拟议的研究将（1）检验以下假设： 外源聚集蛋白聚糖对关键期基质合成的影响 培养软骨细胞的基质积累仅归因于渗透压 聚集蛋白聚糖的特性； (2)如何确定聚集蛋白聚糖或聚集蛋白聚糖的结构 替代品促进组装； (3)确定聚集蛋白聚糖是否促进基质 通过提供物理化学作用在关键过渡阶段进行组装 属性而非结构属性； (4)检查是否存在 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方面的有效性。