| 1. |
- Dahlberg, Leif, et al.
(författare)
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Proteoglycan fragments in joint fluid : Influence of arthrosis and inflammation
- 1992
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Ingår i: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 0001-6470. ; 63:4, s. 417-423
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Tidskriftsartikel (refereegranskat)abstract
- We determined the concentration of proteoglycan fragments in knee joint fluid collected from knee-ligament injured patients more than 6 months after the trauma and from patients with acute pyrophosphate arthritis and arthrosis or with arthrosis only. Injured patients with normal or only mildly altered cartilage at arthroscopy and with normal radiographs, had twice the average concentration of healthy volunteers. Other injured patients with advanced, radiographic signs of arthrosis, had synovial fluid proteoglycan fragment concentrations within the range of healthy volunteers. Patients with pyrophosphate arthritis had the highest concentrations, substantially increased compared with both arthrosis patients, with or without knee injury and healthy volunteers. Likewise, there was an inverse relation between the degree of arthrosis and the concentration of proteoglycan fragments in the joint fluid in patients with pyrophosphate arthritis and arthrosis or with arthrosis only. We conclude that synovial fluid levels of proteoglycan fragments are influenced by the mass of cartilage matrix remaining in the joint, the inflammatory activity in the joint, and the metabolic activity of the cartilage cells.
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| 2. |
- Heathfield, Terrence, et al.
(författare)
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Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal tyrosine sulphate rich region by proteolysis at a site that is sensitive to MMP-13.
- 2004
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 279:8, s. 6286-6295
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Tidskriftsartikel (refereegranskat)abstract
- Integrity of cartilage fails in joint disease. The current work aimed to identify candidate active proteinases in joint diseases using an in vitro model for cartilage degradation induced by interleukin-1. A critical event in the process of cartilage destruction in joint disease is the failure of the collagen fiber network to maintain integrity. Proteins binding to the surface of the fibers are likely early points of failure. Fibromodulin, a member of the leucine-rich repeat protein family, is one predominant protein in cartilage and is known for its roles in the formation of collagen fibrils and sustained interaction with these formed fibers. Cleavage removes the tyrosine sulfate-rich region in the N terminus of fibromodulin. Whereas fibromodulin bound to collagen in tissue was digested, purified fibromodulin was not cleaved. In contrast an N-terminal 10-kDa fragment, Gln19-Lys98, of the protein generated by Lys-C digestion contains the cleavage site and was a substrate cleaved by the enzyme in medium from stimulated cultures. In solution, digestion of this substrate with matrix metalloproteinase (MMP)-2, -9, -8, and -13 demonstrated that only MMP-13 was capable to efficiently cleave it. The cleavage product obtained after MMP-13 digestion was identical to that observed in cleaved fibromodulin from cartilage explant cultures stimulated with interleukin-1. MMP-13 treatment of fresh articular cartilage also produced the fragment under study. The elucidation of the enzyme responsible for such cleavage may lead to treatment modalities involving its selective inhibition for patients suffering from arthritis. The known structure of the fragments permits the generation of neo-epitope antibodies to the cleavage site, which can be used to detect ongoing cartilage degradation in patients with arthritic disease, an important adjunct in monitoring disease progression, active disease, and efficacy of treatment.
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| 3. |
- Lohmander, Stefan, et al.
(författare)
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Increased levels of proteoglycan fragments in knee joint fluid after injury
- 1989
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 32:11, s. 1434-1442
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Tidskriftsartikel (refereegranskat)abstract
- We measured the levels of cartilage proteoglycan (PG) fragments in knee joint synovial fluid obtained from patients with previous trauma of the knee, early gonarthrosis, or pyrophosphate synovitis, and in age-matched control subjects. During the initial 3-4 weeks after rupture of the anterior cruciate ligament or the meniscus (confirmed by arthroscopy), markedly increased PG fragment levels were found. At later times after trauma (up to 4 years), many of these patients still had significantly elevated levels of cartilage PG fragments in the joint fluid. In a group of older patients with gonarthrosis, these levels were only moderately elevated, while in patients with acute pseudogout, greatly increased levels were observed. Although longitudinal studies are needed to validate the significance, PG fragments in joint fluid may be a marker for early posttraumatic arthrosis.
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| 4. |
- Stubendorff, Johann, et al.
(författare)
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Is cartilage sGAG content related to early changes in cartilage disease? Implications for interpretation of dGEMRIC.
- 2012
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 20:5, s. 396-404
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study investigates sulphated glycosaminoglycans (sGAG) content changes in early osteoarthritis (OA), and whether contrast-enhanced magnetic resonance imaging (MRI) of cartilage in vitro may identify early event of OA pathology. METHOD: Osteochondral plugs from patients with hip OA or femoral neck fracture (reference group) were collected and analysed by 1.5 T MRI with ΔR1 as a measure of cartilage contrast concentration. Cartilage hydration, contents of sGAG, cartilage oligomeric matrix protein (COMP), hydroxyproline, denatured collagen, and aggrecan TEGE(392) neoepitope were determined and histological grading was performed. RESULTS: sGAG content correlated to ΔR1, although no difference in either of these parameters was detectable between OA and reference cartilage at 4 h of contrast equilibration. In contrast, biochemical analysis of other cartilage matrix constituents showed distinct alterations typical for early cartilage degradation in OA cartilage and with clear evidence for increased aggrecan turnover. CONCLUSION: In the present in vitro study, cartilage sGAG content could not distinguish between early OA cartilage and reference cartilage. Given, that delayed gadolinium enhanced MRI of cartilage (dGEMRIC) indicates early events in the pathogenesis of OA in vivo, our results from the in vitro studies imply other, additional factors than cartilage sGAG content, e.g., alterations in diffusion or increased supply of contrast agent in the diseased joint. Alternatively, an altered dGEMRIC reflects later stages of OA, when sGAG content decreases. Further investigations are warranted, to understand variations in sGAG content in pathology, an essential background for interpreting dGEMRIC measurements.
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| 5. |
- Åhrman, Emma, et al.
(författare)
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Novel COMP Neoepitopes Identified in Synovial Fluids from Patients with Joint Diseases using Affinity Chromatography and Mass Spectrometry.
- 2014
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 289:30, s. 20908-20916
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Tidskriftsartikel (refereegranskat)abstract
- To identify patients at risk for progressive joint damage there is a need for early diagnostic tools to detect molecular events leading to cartilage destruction. Isolation and characterization of distinct cartilage oligomeric matrix protein (COMP) fragments derived from cartilage and released into synovial fluid will allow discrimination between different pathological conditions and monitoring of disease progression. Early detection of disease and processes in the tissue as well as an understanding of the pathologic mechanisms will also open for novel treatment strategies. Disease specific COMP fragments were isolated by affinity chromatography of synovial fluids from patients with rheumatoid arthritis (RA), osteoarthritis (OA) or acute trauma (AT). Enriched COMP fragments were separated by SDS-PAGE followed by in-gel digestion and mass spectrometric identification and characterization. Using the enzymes trypsin, chymotrypsin and Asp-N for the digestions an extensive analysis of the enriched fragments could be accomplished. Twelve different neoepitopes were identified and characterized within the enriched COMP fragments. For one of the neoepitopes, S77, an inhibition ELISA was developed. This ELISA quantifies COMP fragments clearly distinguishable from total COMP. Furthermore, fragments containing the neoepitope S77 were released into the culture medium of cytokine (TNF-α and IL-6/sIL-6R) stimulated human cartilage explants. The identified neoepitopes provide a complement to the currently available commercial assays for cartilage markers. Through neoepitope assays, tools to pin-point disease progression, evaluation methods for therapy and means to elucidate disease mechanisms will be provided.
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