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Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments.

Struglics, André LU ; Larsson, Staffan LU ; Pratta, M A ; Kumar, S ; Lark, M W and Lohmander, Stefan LU (2006) In Osteoarthritis and Cartilage 14(2). p.101-113
Abstract
Objective: To identify the major aggrecanase-and matrix metalloproteinase (MMP)-generated aggrecan fragments in human osteoarthritis (OA) synovial fluid and in human OA joint cartilage. Method Aggrecan fragments were prepared by CsCl gradient centrifugation. Fragment distributions were compared with aggrecanase-1 (ADAMTS-4) and MMP-3 digested human aggrecan by analysis with neoepitope antibodies and an anti-G1 domain antibody, using Western immuno-blots. Results: The overall fragment pattern of CA synovial fluid aggrecan was similar to the fragment pattern of cartilage aggrecan cleaved in vitro by ADAMTS-4. However, multiple glycosaminoglycan (GAG) containing aggrecanase and MMP-generated aggrecan fragments were identified in OA synovial... (More)
Objective: To identify the major aggrecanase-and matrix metalloproteinase (MMP)-generated aggrecan fragments in human osteoarthritis (OA) synovial fluid and in human OA joint cartilage. Method Aggrecan fragments were prepared by CsCl gradient centrifugation. Fragment distributions were compared with aggrecanase-1 (ADAMTS-4) and MMP-3 digested human aggrecan by analysis with neoepitope antibodies and an anti-G1 domain antibody, using Western immuno-blots. Results: The overall fragment pattern of CA synovial fluid aggrecan was similar to the fragment pattern of cartilage aggrecan cleaved in vitro by ADAMTS-4. However, multiple glycosaminoglycan (GAG) containing aggrecanase and MMP-generated aggrecan fragments were identified in OA synovial fluid and some of these fragments were produced by the action of both types of proteinases. The synovial fluid content of large size aggrecan fragments with (374)ARGS- and (342)FFGV-N-terminals was about 107 and 40 pmoles per ml, respectively, out of a total concentration of aggrecan fragments of about 185 pmoles per ml. CA synovial fluid contained insignificant amounts of the G1-IPEN341 fragment as compared to the G1-TEGE(373) fragment, while CA cartilage contained significant amounts of both fragments. OA cartilage contained several GAG-containing aggrecan fragments with N-terminals of G1- or (342)FFGV- but no fragments with an N-terminal of (374)ARGS-. Conclusions: The overall pattern of aggrecan fragments in human CA synovial fluid and cartilage supports an important role for aggrecanase in aggrecan degradation. However, the fragment patterns and their differential distribution between cartilage and synovial fluid are consistent with the existence of at least two proteolytic pathways for aggrecan degradation in human OA, generating both (342)FFGV- and (374)ARGS-fragments. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved. (Less)
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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
aggrecan, synovial fluid, osteoarthritis, cartilage, matrix metalloproteinase, aggrecanase
in
Osteoarthritis and Cartilage
volume
14
issue
2
pages
101 - 113
publisher
Elsevier
external identifiers
  • pmid:16188468
  • wos:000235240000002
  • scopus:30544448357
ISSN
1063-4584
DOI
10.1016/j.joca.2005.07.018
language
English
LU publication?
yes
id
bd36f3a2-044b-492a-b9a0-6edc89893432 (old id 145046)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16188468&dopt=Abstract
date added to LUP
2016-04-01 12:35:17
date last changed
2020-12-15 02:02:06
@article{bd36f3a2-044b-492a-b9a0-6edc89893432,
  abstract     = {Objective: To identify the major aggrecanase-and matrix metalloproteinase (MMP)-generated aggrecan fragments in human osteoarthritis (OA) synovial fluid and in human OA joint cartilage. Method Aggrecan fragments were prepared by CsCl gradient centrifugation. Fragment distributions were compared with aggrecanase-1 (ADAMTS-4) and MMP-3 digested human aggrecan by analysis with neoepitope antibodies and an anti-G1 domain antibody, using Western immuno-blots. Results: The overall fragment pattern of CA synovial fluid aggrecan was similar to the fragment pattern of cartilage aggrecan cleaved in vitro by ADAMTS-4. However, multiple glycosaminoglycan (GAG) containing aggrecanase and MMP-generated aggrecan fragments were identified in OA synovial fluid and some of these fragments were produced by the action of both types of proteinases. The synovial fluid content of large size aggrecan fragments with (374)ARGS- and (342)FFGV-N-terminals was about 107 and 40 pmoles per ml, respectively, out of a total concentration of aggrecan fragments of about 185 pmoles per ml. CA synovial fluid contained insignificant amounts of the G1-IPEN341 fragment as compared to the G1-TEGE(373) fragment, while CA cartilage contained significant amounts of both fragments. OA cartilage contained several GAG-containing aggrecan fragments with N-terminals of G1- or (342)FFGV- but no fragments with an N-terminal of (374)ARGS-. Conclusions: The overall pattern of aggrecan fragments in human CA synovial fluid and cartilage supports an important role for aggrecanase in aggrecan degradation. However, the fragment patterns and their differential distribution between cartilage and synovial fluid are consistent with the existence of at least two proteolytic pathways for aggrecan degradation in human OA, generating both (342)FFGV- and (374)ARGS-fragments. (c) 2005 OsteoArthritis Research Society International. Published by Elsevier Ltd. All rights reserved.},
  author       = {Struglics, André and Larsson, Staffan and Pratta, M A and Kumar, S and Lark, M W and Lohmander, Stefan},
  issn         = {1063-4584},
  language     = {eng},
  number       = {2},
  pages        = {101--113},
  publisher    = {Elsevier},
  series       = {Osteoarthritis and Cartilage},
  title        = {Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments.},
  url          = {https://lup.lub.lu.se/search/ws/files/2984714/625026.pdf},
  doi          = {10.1016/j.joca.2005.07.018},
  volume       = {14},
  year         = {2006},
}