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Collagen type II/IX/XI heteropolymer assembly

II/IX/XI 型胶原蛋白杂聚物组装体

基本信息

批准号：
7242645
负责人：
RUSSELL J FERNANDES
金额：
$ 7.19万
依托单位：
UNIVERSITY OF WASHINGTON
依托单位国家：
美国
项目类别：
财政年份：
2005
资助国家：
美国
起止时间：
2005-07-01 至 2009-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): The ability of cartilage to withstand mechanical stress depends on the quality of the type II/IX/XI collagen heterofibrillar network that frames cartilage. In arthritis, progressive degradation of this network leads to a loss of normal joint function since cartilage has a limited capacity to heal. In the new field of research, cartilage tissue engineering, which has the ambitious goal of stimulating cartilage repair in vivo or growing cartilage tissue in vitro to resurface or reconstruct joints, it is known that cartilage cells can be induced to synthesize and form a matrix based on type II collagen. To what degree the fibrillar matrix is normal, in terms of the correct assemblies of minor collagens (types IX and XI) with type II collagen is not well characterized. The goal of this study is to use methods in protein chemistry to establish a molecular fingerprint of collagen heterofibril assembly as a biomarker for normal and engineered cartilage. The aim is to investigate the ability of chondrocytes, cultured under suitable conditions or induced with fibroblast growth factor-18, to assemble collagen types II, IX and XI into the co-polymeric cross-linked network that typifies hyaline cartilage in vivo. Since each of the minor collagens is essential in regulating the organization of the network, fingerprinting the pattern of inter-type cross-linking provides a screen for normal matrix assembly. This will be invaluable in understanding the temporal sequence of events in fibrillogenesis of the type II collagen heterofibril and lay the foundation for assessing the changing quality of cartilage in disease, when produced as a healing response or when induced by tissue engineering methods.

描述（由申请人提供）：软骨承受机械应力的能力取决于构成软骨的II/IX/XI型胶原异原纤维网络的质量。在关节炎中，该网络的进行性退化导致正常关节功能的丧失，因为软骨具有有限的愈合能力。在新的研究领域，软骨组织工程，其具有刺激体内软骨修复或体外生长软骨组织以重新表面化或重建关节的雄心勃勃的目标，已知软骨细胞可以被诱导以合成并形成基于II型胶原的基质。就次要胶原蛋白（IX型和XI型）与II型胶原蛋白的正确组装而言，纤维基质正常的程度尚未得到很好的表征。本研究的目的是利用蛋白质化学方法建立胶原异原纤维组装的分子指纹，作为正常和工程软骨的生物标志物。目的是研究在合适的条件下培养或用成纤维细胞生长因子-18诱导的软骨细胞将II型、IX型和XI型胶原组装成体内典型透明软骨的共聚物交联网络的能力。由于每种次要胶原蛋白在调节网络的组织中是必不可少的，因此对类型间交联的模式进行指纹识别为正常的基质组装提供了筛选。这将是非常宝贵的理解的时间序列的事件在原纤维形成的II型胶原蛋白异原纤维，并奠定了基础，评估软骨质量的变化在疾病中，当产生的愈合反应或组织工程方法诱导。