| 1. |
- Struglics, André, et al.
(författare)
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Human osteoarthritis synovial fluid and joint cartilage contain both aggrecanase- and matrix metalloproteinase-generated aggrecan fragments.
- 2006
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 14:2, s. 101-113
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Tidskriftsartikel (refereegranskat)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.
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| 2. |
- Dahlberg, L., et al.
(författare)
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A longitudinal study of cartilage matrix metabolism in patients with cruciate ligament rupture-synovial fluid concentrations of aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinase-1
- 1994
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Ingår i: British Journal of Rheumatology. - : Oxford University Press (OUP). - 0263-7103. ; 33:12, s. 1107-1111
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Tidskriftsartikel (refereegranskat)abstract
- This is the first study which quantifies aggrecan fragments, stromelysin-1 and tissue inhibitor of metalloproteinases-1 (TIMP-1) in SF samples prospectively obtained from the same patient at different time intervals after a cruciate ligament injury of the knee. Aggrecan fragment concentrations were determined by dye precipitation with Alcian Blue. Stromelysin-1 and TIMP-1 were analysed by immunoassay. Ten healthy volunteers formed the reference group. Immediately after knee injury, all marker concentrations were higher as compared to the reference group. The high marker concentrations decreased gradually with time, and in samples obtained between 6 months and 6 years after the injury, median concentrations of some of the markers were not different compared to reference levels. This was in contrast to results from previous cross-sectional studies, where chronic phase median concentrations of all markers were consistently higher than reference levels. In previous cross-sectional studies, however, the samples were obtained at arthroscopy done because of knee complaints at different times after a knee injury. In the present study, the knee injured patients visited the orthopaedic outpatient ward only for SF sampling, and they had no or only minor knee symptoms. We conclude that the temporal changes of marker concentrations in joint fluid after knee injury, suggested from cross-sectional studies, have now been confirmed in a longitudinal, prospective cohort study. We further find that in patients with mild knee symptoms in the chronic phase after cruciate ligament injury, median SF levels of aggrecan fragments, stromelysin-1, and TIMP-1 are lower than in patients with significant knee complaints after the same type of injury. This suggests a possible relationship between joint fluid marker concentrations, joint pathology, and cartilage metabolism.
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| 3. |
- Dahlberg, L., et al.
(författare)
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Authors' reply
- 1995
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967. ; 54:8, s. 685-685
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Tidskriftsartikel (refereegranskat)
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| 4. |
- Dahlberg, L., et al.
(författare)
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Cartilage metabolism in the injured and uninjured knee of the same patient
- 1994
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967. ; 53:12, s. 823-827
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Tidskriftsartikel (refereegranskat)abstract
- Objective-To examine if unilateral knee injury affects the synovial fluid concentrations of aggrecan fragments, cartilage oligomeric matrix protein (COMP) fragments, stromelysin-l, and tissue inhibitor of metalloproteinases-l (TIMP-1) in the contralateral uninjured knee. Methods-Synovial fluids from the injured and uninjured knees were obtained at different times in a group of patients after unilateral knee trauma. Serum samples were obtained on the same occasion. Concentrations of aggrecan fragments were determined by precipitation with Alcian Blue; those of COMP fragments, stromelysin-l, and TIMP-1 were measured by immunoassay. Concentrations were compared with those in a reference group of 10 healthy volunteers. Results-Immediately after knee injury, concentrations of aggrecan fragments, COMP fragments, stromelysin-l and TIMP-1 were increased in the synovial fluid of the injured knee. However, concentrations of aggrecan and COMP fragments, and stromelysin-l increased also in the contralateral uninjured knee immediately after injury, but less than in the injured knee. Subsequently, the concentrations ofall markers decreased in the synovial fluid of the injured knee, but remained unchanged in the uninjured knee. The concentration of aggrecan fragments in the injured knee decreased to less than that in the uninjured knee in the chronic phase. Serum concentrations of COMP were much smaller than those in synovial fluid. Conclusions-The increased concentrations of aggrecan and COMP fragments and stromelysin-1 in the joint fluid of the contralateral, uninjured knee following unilateral knee injury, compared with concentrations in healthy reference knees, suggest changes in joint cartilage metabolism in both knees following unilateral knee injury. The mechanisms for these changes are unclear. The low serum concentration of COMP makes it less likely that there is any significant 'exchange' of molecular markers between the knees. A further consequence of these findings is that the contralateral knee cannot be recommended as the only control joint in studies of matrix metabolism in patients with unilateral knee injury.
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| 5. |
- Lohmander, L. S., et al.
(författare)
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Stromelysin, tissue inhibitor of metalloproteinases and proteoglycan fragments in human knee joint fluid after injury
- 1993
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 20:8, s. 1362-1368
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine in a cross sectional study the concentrations of stromelysin, tissue inhibitor of metalloproteinases (TIMP), and proteoglycan fragments in knee synovial fluid (SF) at different times after injury to cruciate ligament or meniscus. Methods. Joint fluid samples were obtained from patients with knee injury diagnosed by arthroscopy. Concentrations of stromelysin-1 and TIMP-1 were determined by immunoassay with monoclonal and polyclonal antibodies. Cartilage proteoglycan fragments were quantified by immunoassay with polyclonal antibodies or by dye precipitation. Results. Average concentrations of stromelysin increased 40-fold in association with injury, and after about 6 months decreased to a plateau level about 10-fold increased compared to a reference group with healthy knees. TIMP and proteoglycan levels also increased in similar temporal patterns, but less markedly. Increased average SF levels of these markers were maintained for at least 17 years after injury. SF from knees with injury contained a 1.5 to 2.5 molar excess of stromelysin over TIMP, while reference joint fluids contained a 2-fold molar excess of TIMP over stromelysin. Conclusion. The persistent changes in SF markers after joint injury may be associated with the cartilage destruction and frequent development of posttraumatic osteoarthritis in this group of patients.
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| 6. |
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