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Changes in joint cartilage aggrecan after knee injury and in osteoarthritis

Lohmander, L. Stefan LU ; Ionescu, Mirela; Jugessur, Hitu and Poole, A. Robin (1999) In Arthritis and Rheumatism 42(3). p.534-544
Abstract

Objective. To determine the concentrations of aggrecan fragments in synovial fluid from patients with knee joint injury, osteoarthritis (OA), or acute pyrophosphate arthritis (PPA; pseudogout), and to test their relative reactivity with the 846 epitope, a putative marker of cartilage aggrecan synthesis. Methods. Samples of knee joint fluid from 385 patients and 9 healthy-knee volunteers were obtained in a cross-sectional study. Study groups were acute PPA/pseudogout (n = 60), anterior cruciate ligament (ACL) rupture (n = 159), meniscus lesion (n = 129), and primary knee OA (n = 37). The 846 epitope on aggrecan was assayed by competitive solution-phase radioimmunoassay. Aggrecan fragments were assayed by enzyme-linked immunosorbent assay... (More)

Objective. To determine the concentrations of aggrecan fragments in synovial fluid from patients with knee joint injury, osteoarthritis (OA), or acute pyrophosphate arthritis (PPA; pseudogout), and to test their relative reactivity with the 846 epitope, a putative marker of cartilage aggrecan synthesis. Methods. Samples of knee joint fluid from 385 patients and 9 healthy-knee volunteers were obtained in a cross-sectional study. Study groups were acute PPA/pseudogout (n = 60), anterior cruciate ligament (ACL) rupture (n = 159), meniscus lesion (n = 129), and primary knee OA (n = 37). The 846 epitope on aggrecan was assayed by competitive solution-phase radioimmunoassay. Aggrecan fragments were assayed by enzyme-linked immunosorbent assay using a monoclonal antibody (1-F21). Cartilage oligomeric matrix protein (COMP), C-propeptide of type II collagen (CPII), bone sialoprotein, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were previously quantified by immunoassays. Results. Reactivity of the 846 epitope was increased in all study groups compared with the reference group, and was highest in patients with primary OA. The median levels (in μg fetal aggrecan equivalents/ml) of the epitope were 0.28 (range 0.24-0.47) in the reference group, 0.48 (range 0.26-1.32) in PPA/pseudogout, 0.61 (range 0.12-2.87) in ACL rupture, 0.53 (range 0.22-3.02) in meniscus lesion, and 0.68 (range 0.31-4.31) in primary OA. The 846 epitope reactivity per μg aggrecan fragments in the joint fluid was higher in late-stage OA than in early-stage OA. Epitope 846 reactivity correlated positively with several markers of matrix turnover, particularly with COMP (r(s) = 0.421) and CPII (r(s) = 0.307). Conclusion. The observed differences in 846 epitope reactivity in synovial fluid, and its concentration in relation to aggrecan and other markers of matrix turnover, were consistent with marked ongoing changes in aggrecan turnover after joint injury and in the development of OA. OA is thus a disease characterized by dynamic changes in tissue macromolecule turnover, which is reflected by measurable changes in aggrecan epitopes in the synovial fluid.

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author
publishing date
type
Contribution to journal
publication status
published
in
Arthritis and Rheumatism
volume
42
issue
3
pages
11 pages
publisher
John Wiley & Sons
external identifiers
  • Scopus:0033050802
ISSN
0004-3591
DOI
10.1002/1529-0131(199904)42:3<534::AID-ANR19>3.0.CO;2-J
language
English
LU publication?
no
id
c2d7de30-c91d-4175-882a-d81e5af78f10
date added to LUP
2016-05-05 11:33:58
date last changed
2016-11-06 04:37:40
@misc{c2d7de30-c91d-4175-882a-d81e5af78f10,
  abstract     = {<p>Objective. To determine the concentrations of aggrecan fragments in synovial fluid from patients with knee joint injury, osteoarthritis (OA), or acute pyrophosphate arthritis (PPA; pseudogout), and to test their relative reactivity with the 846 epitope, a putative marker of cartilage aggrecan synthesis. Methods. Samples of knee joint fluid from 385 patients and 9 healthy-knee volunteers were obtained in a cross-sectional study. Study groups were acute PPA/pseudogout (n = 60), anterior cruciate ligament (ACL) rupture (n = 159), meniscus lesion (n = 129), and primary knee OA (n = 37). The 846 epitope on aggrecan was assayed by competitive solution-phase radioimmunoassay. Aggrecan fragments were assayed by enzyme-linked immunosorbent assay using a monoclonal antibody (1-F21). Cartilage oligomeric matrix protein (COMP), C-propeptide of type II collagen (CPII), bone sialoprotein, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases 1 were previously quantified by immunoassays. Results. Reactivity of the 846 epitope was increased in all study groups compared with the reference group, and was highest in patients with primary OA. The median levels (in μg fetal aggrecan equivalents/ml) of the epitope were 0.28 (range 0.24-0.47) in the reference group, 0.48 (range 0.26-1.32) in PPA/pseudogout, 0.61 (range 0.12-2.87) in ACL rupture, 0.53 (range 0.22-3.02) in meniscus lesion, and 0.68 (range 0.31-4.31) in primary OA. The 846 epitope reactivity per μg aggrecan fragments in the joint fluid was higher in late-stage OA than in early-stage OA. Epitope 846 reactivity correlated positively with several markers of matrix turnover, particularly with COMP (r(s) = 0.421) and CPII (r(s) = 0.307). Conclusion. The observed differences in 846 epitope reactivity in synovial fluid, and its concentration in relation to aggrecan and other markers of matrix turnover, were consistent with marked ongoing changes in aggrecan turnover after joint injury and in the development of OA. OA is thus a disease characterized by dynamic changes in tissue macromolecule turnover, which is reflected by measurable changes in aggrecan epitopes in the synovial fluid.</p>},
  author       = {Lohmander, L. Stefan and Ionescu, Mirela and Jugessur, Hitu and Poole, A. Robin},
  issn         = {0004-3591},
  language     = {eng},
  number       = {3},
  pages        = {534--544},
  publisher    = {ARRAY(0xa800de0)},
  series       = {Arthritis and Rheumatism},
  title        = {Changes in joint cartilage aggrecan after knee injury and in osteoarthritis},
  url          = {http://dx.doi.org/10.1002/1529-0131(199904)42:3<534::AID-ANR19>3.0.CO;2-J},
  volume       = {42},
  year         = {1999},
}