Abstract | INTRODUCTION:
Aggrecanase cleavage at the 392Glu-393Ala bond in the interglobular domain ( IGD) of aggrecan, releasing N-terminal 393ARGS fragments, is an early key event in arthritis and joint injuries. Here, we use a quantitative immunoassay of aggrecan ARGS neoepitope fragments in human synovial fluid to determine if this cleavage-site specific method better identifies joint pathology than previously available less specific aggrecan assays. METHODS: RESULTS:
Aggrecan ARGS fragment concentrations in all groups differed from the reference group (P < 0.001). The acute inflammatory arthritis group had the highest median level, 177-fold greater than that of the reference group. Median levels (in pmol ARGS/ml SF) were: reference 0.5, acute inflammatory arthritis 88.5, acute knee injury 53.9, chronic knee injury 0.5 and OA 4.6. In contrast, aggrecan and sulfated glycosaminoglycan concentrations varied much less between groups, and only acute inflammatory arthritis and acute knee injury were found to have a two-fold increase in median levels compared to the reference. CONCLUSIONS: Levels of aggrecan ARGS fragments in human synovial fluid are increased in human arthritis, OA and after knee injury, likely reflecting an enhanced cleavage at the 392Glu-393Ala bond in the IGD by aggrecanase. An assay that specifically quantified these fragments better distinguished samples from joints with pathology than assays monitoring aggrecan or glycosaminoglycan concentrations. The newly developed ARGS fragment assay can be used to monitor aggrecanase activity in human joint disease and experimental models.
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Authors | Staffan Larsson, L Stefan Lohmander, André Struglics |
Journal | Arthritis research & therapy
(Arthritis Res Ther)
Vol. 11
Issue 3
Pg. R92
( 2009)
ISSN: 1478-6362 [Electronic] England |
PMID | 19545413
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Aggrecans
- Biomarkers
- Epitopes
- Glycosaminoglycans
- Peptide Fragments
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Topics |
- Adolescent
- Adult
- Aged
- Aged, 80 and over
- Aggrecans
(analysis, metabolism)
- Biomarkers
(analysis, metabolism)
- Cohort Studies
- Cross-Sectional Studies
- Epitopes
(analysis, metabolism)
- Female
- Glycosaminoglycans
(analysis, metabolism)
- Humans
- Joint Diseases
(diagnosis, metabolism)
- Male
- Middle Aged
- Peptide Fragments
(analysis, metabolism)
- Synovial Fluid
(chemistry, metabolism)
- Young Adult
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