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Human aggrecanase generated synovial fluid fragment levels are elevated directly after knee injuries due to proteolysis both in the inter globular and chondroitin sulfate domains.

Struglics, André LU ; Björklund, Maria LU and Lohmander, Stefan LU (2011) In Osteoarthritis and Cartilage 19. p.1047-1057
Abstract
OBJECTIVE: To examine different aggrecanase generated fragments in synovial fluid (SF) from patients with acute and chronic knee injuries and from knee healthy subjects. METHODS: We prepared SF-D1 samples from acute (n=35) and chronic (n=35) knee injury patients and knee healthy subjects (n=10). Aggrecan fragments were analyzed in the SF-D1 samples by quantitative (G1, ARGS, KEEE and G3 antibodies) and non-quantitative (GRGT and AGEG antibodies) Western blot. RESULTS: ARGS-SELE, ARGS-chondroitin sulfate (CS)1, GRGT-, GLGS- and AGEG-G3 fragments were the main ARGS and G3 fragments in injured and reference samples. In the acute injury samples the concentrations of these fragments were increased compared to the reference, and the level of the... (More)
OBJECTIVE: To examine different aggrecanase generated fragments in synovial fluid (SF) from patients with acute and chronic knee injuries and from knee healthy subjects. METHODS: We prepared SF-D1 samples from acute (n=35) and chronic (n=35) knee injury patients and knee healthy subjects (n=10). Aggrecan fragments were analyzed in the SF-D1 samples by quantitative (G1, ARGS, KEEE and G3 antibodies) and non-quantitative (GRGT and AGEG antibodies) Western blot. RESULTS: ARGS-SELE, ARGS-chondroitin sulfate (CS)1, GRGT-, GLGS- and AGEG-G3 fragments were the main ARGS and G3 fragments in injured and reference samples. In the acute injury samples the concentrations of these fragments were increased compared to the reference, and the level of the ARGS-SELE remained elevated for at least 2 years after the joint injury. Both SF ARGS fragments and aggrecanase generated G3 fragments had high sensitivity and specificity as biomarkers in distinguishing injured from healthy knee joints, although the ARGS fragments had higher area under the receiver operating characteristic curve (AUC) values for injuries (74-86%) than the G3 fragments (AUC values 63-68%). CONCLUSION: Our results suggest that during the acute phase after knee injury there is an increased aggrecanase activity against both the interglobular domain (IGD) and the CS2 cleavage sites of joint cartilage aggrecan. This increase in SF aggrecanolytic fragments is present for several years after the injury. SF ARGS fragments are better biomarkers than the aggrecanase generated G3-fragments in distinguishing injured from healthy knee joints. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Osteoarthritis and Cartilage
volume
19
pages
1047 - 1057
publisher
Elsevier
external identifiers
  • wos:000294240400015
  • pmid:21664283
  • scopus:79960325801
ISSN
1063-4584
DOI
10.1016/j.joca.2011.05.006
language
English
LU publication?
yes
id
d6a6fd5e-6dbf-4c84-97ec-eb54a0de6d38 (old id 2008196)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21664283?dopt=Abstract
date added to LUP
2011-07-04 13:42:20
date last changed
2017-07-23 04:54:32
@article{d6a6fd5e-6dbf-4c84-97ec-eb54a0de6d38,
  abstract     = {OBJECTIVE: To examine different aggrecanase generated fragments in synovial fluid (SF) from patients with acute and chronic knee injuries and from knee healthy subjects. METHODS: We prepared SF-D1 samples from acute (n=35) and chronic (n=35) knee injury patients and knee healthy subjects (n=10). Aggrecan fragments were analyzed in the SF-D1 samples by quantitative (G1, ARGS, KEEE and G3 antibodies) and non-quantitative (GRGT and AGEG antibodies) Western blot. RESULTS: ARGS-SELE, ARGS-chondroitin sulfate (CS)1, GRGT-, GLGS- and AGEG-G3 fragments were the main ARGS and G3 fragments in injured and reference samples. In the acute injury samples the concentrations of these fragments were increased compared to the reference, and the level of the ARGS-SELE remained elevated for at least 2 years after the joint injury. Both SF ARGS fragments and aggrecanase generated G3 fragments had high sensitivity and specificity as biomarkers in distinguishing injured from healthy knee joints, although the ARGS fragments had higher area under the receiver operating characteristic curve (AUC) values for injuries (74-86%) than the G3 fragments (AUC values 63-68%). CONCLUSION: Our results suggest that during the acute phase after knee injury there is an increased aggrecanase activity against both the interglobular domain (IGD) and the CS2 cleavage sites of joint cartilage aggrecan. This increase in SF aggrecanolytic fragments is present for several years after the injury. SF ARGS fragments are better biomarkers than the aggrecanase generated G3-fragments in distinguishing injured from healthy knee joints.},
  author       = {Struglics, André and Björklund, Maria and Lohmander, Stefan},
  issn         = {1063-4584},
  language     = {eng},
  pages        = {1047--1057},
  publisher    = {Elsevier},
  series       = {Osteoarthritis and Cartilage},
  title        = {Human aggrecanase generated synovial fluid fragment levels are elevated directly after knee injuries due to proteolysis both in the inter globular and chondroitin sulfate domains.},
  url          = {http://dx.doi.org/10.1016/j.joca.2011.05.006},
  volume       = {19},
  year         = {2011},
}