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Cartilage destruction - Release of type IX collagen in joint disease

Danfelter, Mikael LU (2008) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2008:24.
Abstract
Cartilage is of vital importance for the function of joints. It is characterized by a prominent extracellular matrix (ECM) that is produced and maintained by relatively few cells of one type, the chondrocyte. The cartilage ECM consists of collagen fibrillar networks, proteoglycan aggregates, and a number of other molecules united in numerous interactions. This work focused at identifying catabolic events leading to cartilage destruction and functional impairment and developing tools to detect such events in patients.

In the first part, using a model for cartilage degradation in disease, N-terminal fragments of type IX collagen was found to be released at an intermediate time point. The two most abundant fragments were further... (More)
Cartilage is of vital importance for the function of joints. It is characterized by a prominent extracellular matrix (ECM) that is produced and maintained by relatively few cells of one type, the chondrocyte. The cartilage ECM consists of collagen fibrillar networks, proteoglycan aggregates, and a number of other molecules united in numerous interactions. This work focused at identifying catabolic events leading to cartilage destruction and functional impairment and developing tools to detect such events in patients.

In the first part, using a model for cartilage degradation in disease, N-terminal fragments of type IX collagen was found to be released at an intermediate time point. The two most abundant fragments were further studied and their novel C-terminals identified. These two fragments comprise most of the NC4 domain and the combined NC4 + COL3 domains, respectively. Furthermore, the identified cleavage sites were shown to be induced by matrix metalloproteinase 13 (MMP-13).

In the second part, the potential degradation of type IX collagen in human cartilage was investigated. It was shown that two similar type IX collagen fragments were released from cartilage explants upon MMP-13 digestion. The novel C-terminal of the fragment comprising the NC4 domain was identified. The cleavage site was found to differ between human and bovine type IX collagen. An antiserum raised against the human C-terminal neoepitope confirmed the cleavage and was used to develop an immunoassay (inhibition ELISA). This assay was used to detect elevated levels of the neoepitope in sera from arthritis patients compared to controls, indicating that this cleavage occurs in joint pathology. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Professor Eyre, David R, University of Washington, Seattle, USA
organization
publishing date
type
Thesis
publication status
published
subject
keywords
cartilage destruction, matrix metalloproteinase 13, ECM, assay, neoepitope, NC4 domain, Type IX collagen, fragment
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2008:24
pages
108 pages
publisher
Department of Experimental Medical Science, Lund Univeristy
defense location
Segerfalk lecture hall, Wallenberg Neurocentrum, BMC, Sölvegatan 17, Lund
defense date
2008-03-17 09:00
ISSN
1652-8220
ISBN
978-91-85897-77-3
language
English
LU publication?
yes
id
82b003d0-94fe-4649-9558-17ca1d64a57c (old id 1038220)
date added to LUP
2008-02-26 11:35:00
date last changed
2016-09-19 08:44:46
@phdthesis{82b003d0-94fe-4649-9558-17ca1d64a57c,
  abstract     = {Cartilage is of vital importance for the function of joints. It is characterized by a prominent extracellular matrix (ECM) that is produced and maintained by relatively few cells of one type, the chondrocyte. The cartilage ECM consists of collagen fibrillar networks, proteoglycan aggregates, and a number of other molecules united in numerous interactions. This work focused at identifying catabolic events leading to cartilage destruction and functional impairment and developing tools to detect such events in patients.<br/><br>
	In the first part, using a model for cartilage degradation in disease, N-terminal fragments of type IX collagen was found to be released at an intermediate time point. The two most abundant fragments were further studied and their novel C-terminals identified. These two fragments comprise most of the NC4 domain and the combined NC4 + COL3 domains, respectively. Furthermore, the identified cleavage sites were shown to be induced by matrix metalloproteinase 13 (MMP-13). <br/><br>
	In the second part, the potential degradation of type IX collagen in human cartilage was investigated. It was shown that two similar type IX collagen fragments were released from cartilage explants upon MMP-13 digestion. The novel C-terminal of the fragment comprising the NC4 domain was identified. The cleavage site was found to differ between human and bovine type IX collagen. An antiserum raised against the human C-terminal neoepitope confirmed the cleavage and was used to develop an immunoassay (inhibition ELISA). This assay was used to detect elevated levels of the neoepitope in sera from arthritis patients compared to controls, indicating that this cleavage occurs in joint pathology.},
  author       = {Danfelter, Mikael},
  isbn         = {978-91-85897-77-3},
  issn         = {1652-8220},
  keyword      = {cartilage destruction,matrix metalloproteinase 13,ECM,assay,neoepitope,NC4 domain,Type IX collagen,fragment},
  language     = {eng},
  pages        = {108},
  publisher    = {Department of Experimental Medical Science, Lund Univeristy},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Cartilage destruction - Release of type IX collagen in joint disease},
  volume       = {2008:24},
  year         = {2008},
}