Collagen type II/IX/XI heteropolymer assembly

点击翻译按钮获取中文摘要

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.