Cartilage homeostasis: Modulation of cells and extracelllar matrix assembly
(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:
https://lup.lub.lu.se/record/466912
- author
- Johnson, Anna LU
- supervisor
- opponent
-
- Prof. Caterson, Bruce, Connective Tissue Biology Research Group, Cardiff School of Biosciences, Cardiff, Wales. UK
- organization
- publishing date
- 2004
- 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 10:15:00
- ISBN
- 91-628-6085-2
- language
- English
- LU publication?
- yes
- additional info
- Article: I. Fibronectin fragments cause release and degradation of collagen-binding molecules from equine explant culturesAnna Johnson, Roger Smith, Tore Saxne, Mark Hickery and Dick HeinegårdOsteoarthritis Cartilage. 2004 Feb;12 (2):149-59. Article: II. Cellular responses upon binding to chondroadherinAnna Johnson, Henric Olsson, Dick HeinegårdIn manuscript Article: III. Cartilage chondroitin sulphate-substituted perlecan facilitates collagen fibril formationAnna Johnson, Alexander Kvist, Matthias Mörgelin, Erika Gustafsson, Eva Bengtsson, Karin Lindblom, Attila Aszódi, Reinhard Fässler, Rupert Timpl, Dick Heingård , Anders AspbergIn manuscript The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Department of Experimental Medical Science (013210000), Pathology, (Lund) (013030000)
- id
- bbb07c96-2a97-4078-9f2d-c43a192de645 (old id 466912)
- date added to LUP
- 2016-04-04 11:04:52
- date last changed
- 2018-11-21 21:02:32
@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}},
keywords = {{Medicine (human and vertebrates); COMP; Perlecan; chondroadherin; cartilage; ECM; Medicin (människa och djur)}},
language = {{eng}},
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}},
}