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Cartilage homeostasis: Modulation of cells and extracelllar matrix assembly

Johnson, Anna LU (2004)
Abstract
The cartilage extracellular matrix consists of the collagen network which enmeshes the large aggregating proteoglycan, aggrecan. Accessory molecules regulate the formation and maintenance of these structures. This thesis studies aspects of cartilage assembly during development and its degradation in disease, focusing on the collagen network. In the first paper, a model of cartilage degradation is studied. Two molecules with collagen-binding capacity, cartilage oligomeric matrix protein (COMP) and chondroadherin, are released. The early release and the degradation of these components may reflect early stages in disease and is initiated by a fragment of a molecule putatively present in the joint. It may represent initial steps in loosening... (More)
The cartilage extracellular matrix consists of the collagen network which enmeshes the large aggregating proteoglycan, aggrecan. Accessory molecules regulate the formation and maintenance of these structures. This thesis studies aspects of cartilage assembly during development and its degradation in disease, focusing on the collagen network. In the first paper, a model of cartilage degradation is studied. Two molecules with collagen-binding capacity, cartilage oligomeric matrix protein (COMP) and chondroadherin, are released. The early release and the degradation of these components may reflect early stages in disease and is initiated by a fragment of a molecule putatively present in the joint. It may represent initial steps in loosening of the collagen network. Chondroadherin is an integrin-binding protein, and the release observed in Paper I may lead to a change in signaling to the chondrocytes. In the second paper cell studies of responses to binding to chondroadherin demonstrated modulated intracellular signaling and altered synthesis and secretion of some proteins. During development, cartilage is laid down as a template for bone. The third paper describes a novel role for chondroitin sulphated perlecan in the organization of cartilage in development, by organizing collagen. CS-substituted perlecan is shown to facilitate collagen fibrillogenesis, as does the freed CS-chain. Perlecan substituted with heparan sulphate does not display this activity. This finding offers a mechanism for the observed skeletal defects in perlecan-null mice and a novel mechanism for catalyzing collagen fibril formation in tissue. (Less)
Please use this url to cite or link to this publication:
author
opponent
  • Prof. Caterson, Bruce, Connective Tissue Biology Research Group, Cardiff School of Biosciences, Cardiff, Wales. UK
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Medicine (human and vertebrates), COMP, Perlecan, chondroadherin, cartilage, ECM, Medicin (människa och djur)
pages
158 pages
publisher
Dept of Connective Tissue Biology, BMC C12, SE-221 85 Lund,
defense location
Segerfalkssalen,Wallenberg Neurocentrum
defense date
2004-05-18 10:15
ISBN
91-628-6085-2
language
English
LU publication?
yes
id
bbb07c96-2a97-4078-9f2d-c43a192de645 (old id 466912)
date added to LUP
2007-09-07 14:02:09
date last changed
2016-09-19 08:45:08
@phdthesis{bbb07c96-2a97-4078-9f2d-c43a192de645,
  abstract     = {The cartilage extracellular matrix consists of the collagen network which enmeshes the large aggregating proteoglycan, aggrecan. Accessory molecules regulate the formation and maintenance of these structures. This thesis studies aspects of cartilage assembly during development and its degradation in disease, focusing on the collagen network. In the first paper, a model of cartilage degradation is studied. Two molecules with collagen-binding capacity, cartilage oligomeric matrix protein (COMP) and chondroadherin, are released. The early release and the degradation of these components may reflect early stages in disease and is initiated by a fragment of a molecule putatively present in the joint. It may represent initial steps in loosening of the collagen network. Chondroadherin is an integrin-binding protein, and the release observed in Paper I may lead to a change in signaling to the chondrocytes. In the second paper cell studies of responses to binding to chondroadherin demonstrated modulated intracellular signaling and altered synthesis and secretion of some proteins. During development, cartilage is laid down as a template for bone. The third paper describes a novel role for chondroitin sulphated perlecan in the organization of cartilage in development, by organizing collagen. CS-substituted perlecan is shown to facilitate collagen fibrillogenesis, as does the freed CS-chain. Perlecan substituted with heparan sulphate does not display this activity. This finding offers a mechanism for the observed skeletal defects in perlecan-null mice and a novel mechanism for catalyzing collagen fibril formation in tissue.},
  author       = {Johnson, Anna},
  isbn         = {91-628-6085-2},
  keyword      = {Medicine (human and vertebrates),COMP,Perlecan,chondroadherin,cartilage,ECM,Medicin (människa och djur)},
  language     = {eng},
  pages        = {158},
  publisher    = {Dept of Connective Tissue Biology, BMC C12, SE-221 85 Lund,},
  school       = {Lund University},
  title        = {Cartilage homeostasis: Modulation of cells and extracelllar matrix assembly},
  year         = {2004},
}