Collagen type II/IX/XI heteropolymer assembly

II/IX/XI 型胶原蛋白杂聚物组装体

• 批准号: 7087978
• 负责人: RUSSELL J FERNANDES
• 金额: $ 7.4万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7087978
• 关键词: SDS polyacrylamide gel electrophoresis; biomarker; biomechanics; biotechnology; cartilage development; chondrocytes; collagen; copolymer; extracellular matrix; fibroblast growth factor; fibrogenesis; human tissue; mass spectrometry; tissue /cell culture; tissue engineering; western blottings

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型胶原异质纤维网络的质量。在关节炎中，由于软骨的愈合能力有限，该网络的进行性退化会导致正常关节功能的丧失。在软骨组织工程这个新的研究领域，人们已经知道可以诱导软骨细胞合成并形成以II型胶原为基础的基质。软骨组织工程的目标是在体内刺激软骨修复或在体外培养软骨组织，以重建关节表面或重建关节。就小胶原(IX和XI型)与II型胶原的正确组合而言，纤维基质的正常程度尚未得到很好的描述。本研究的目的是利用蛋白质化学的方法建立胶原异质纤维组装的分子指纹图谱，作为正常和工程化软骨的生物标志物。目的是研究在适当条件下培养或在成纤维细胞生长因子-18诱导下培养的软骨细胞将II型、I型和XI型胶原组装成体内典型的透明软骨的共聚交联网络的能力。由于每一种次要的胶原蛋白在调节网络的组织中都是必不可少的，因此对类型间的交联型图案进行指纹分析为正常的基质组装提供了一个屏幕。这对于了解II型胶原异质纤维形成过程中的时间序列是非常有价值的，并为评估疾病中软骨质量的变化奠定了基础，无论是作为愈合反应产生的软骨，还是由组织工程方法诱导的软骨。