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MMP proteolysis of the human extracellular matrix protein aggrecan is mainly a process of normal turnover

Struglics, André LU and Björklund, Maria LU (2012) In Biochemical Journal 446. p.213-223
Abstract
Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS I region, and the border between the CS2... (More)
Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS I region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less-active role in aggrecan degradation during knee injury and OA. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aggrecan, cartilage, degradation, matrix metalloproteinase, proteolysis, synovial fluid
in
Biochemical Journal
volume
446
pages
213 - 223
publisher
Portland Press Limited
external identifiers
  • wos:000308767500005
  • scopus:84865165620
ISSN
0264-6021
DOI
10.1042/BJ20120274
language
English
LU publication?
yes
id
dc589088-7d76-4f2e-a49e-96efd1a9cbc7 (old id 3187992)
date added to LUP
2012-12-06 12:04:17
date last changed
2017-10-29 03:52:23
@article{dc589088-7d76-4f2e-a49e-96efd1a9cbc7,
  abstract     = {Although it has been shown that aggrecanases are involved in aggrecan degradation, the role of MMP (matrix metalloproteinase) aggrecanolysis is less well studied. To investigate MMP proteolysis of human aggrecan, in the present study we used neoepitope antibodies against MMP cleavage sites and Western blot analysis to identify MMP-generated fragments in normal and OA (osteoarthritis/osteoarthritic) cartilage, and in normal, knee injury and OA and SF (synovial fluid) samples. MMP-3 in vitro digestion showed that aggrecan contains six MMP cleavage sites, in the IGD (interglobular domain), the KS (keratan sulfate) region, the border between the KS region and CS (chondroitin sulfate) region 1, the CS I region, and the border between the CS2 and the G3 domain, and kinetic studies showed a specific order of digestion where the cleavage between CS2 and the G3 domain was the most preferred. In vivo studies showed that OA cartilage contained (per dry weight) 3.4-fold more MMP-generated FFGV fragments compared with normal cartilage, and although aggrecanase-generated SF-ARGS concentrations were increased 14-fold in OA and knee-injured patients compared with levels in knee-healthy reference subjects, the SF-FFGV concentrations did not notably change. The results of the present study suggest that MMPs are mainly involved in normal aggrecan turnover and might have a less-active role in aggrecan degradation during knee injury and OA.},
  author       = {Struglics, André and Björklund, Maria},
  issn         = {0264-6021},
  keyword      = {aggrecan,cartilage,degradation,matrix metalloproteinase,proteolysis,synovial fluid},
  language     = {eng},
  pages        = {213--223},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {MMP proteolysis of the human extracellular matrix protein aggrecan is mainly a process of normal turnover},
  url          = {http://dx.doi.org/10.1042/BJ20120274},
  volume       = {446},
  year         = {2012},
}