| 51. |
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| 52. |
- Hauser, Nik, et al.
(författare)
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Interaction of cartilage matrix protein with aggrecan. Increased covalent cross-linking with tissue maturation
- 1996
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 271:50, s. 32247-32252
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage matrix protein (CMP) is a trimeric protein present in many types of cartilage extracellular matrix. It has recently been purified under native conditions that allowed the proposal of a structural model (Hauser, N., and Paulsson, M. (1994) J. Biol. Chem. 269, 25747-25753). To examine the functional properties of CMP we studied its interaction with aggrecan within cartilage extracellular matrix. Aggrecan-enriched fractions were purified from bovine tracheal cartilage of different ages under nondenaturing and denaturing conditions, respectively, and characterized by a combination of biochemical methods and electron microscopy. The fractions contained a pool of CMP noncovalently associated with aggrecan as well as a pool of CMP that appears covalently cross-linked to the aggrecan core protein. Only about two thirds of the CMP subunits could be released even upon reduction under denaturing conditions. It appears that CMP is attached by a nonreducible covalent interaction of one of its subunits with the protein core. The amount of CMP strongly bound to aggrecan increases with age. Electron microscopy revealed interaction sites for CMP in the extended chondroitin-sulfate attachment domain E2. In old tissue five distinct binding sites for CMP were found while in young cartilage only three of these were occupied. The extent of decoration of E2 with CMP increases with age.
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| 53. |
- 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
-
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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| 54. |
- Heinegård, Dick, et al.
(författare)
-
Articular cartilage
- 2014. - 6
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Ingår i: Rheumatology. - 9780323091381 ; , s. 33-41
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 55. |
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| 56. |
- Heinegård, Dick, et al.
(författare)
-
Cartilage matrix destruction
- 2007
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Ingår i: Bone and Osteoarthritis. - 9781846285134
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 57. |
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| 58. |
- Heinegård, Dick, et al.
(författare)
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Cartilage proteoglycans in degenerative joint disease.
- 1987
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 14 (suppl 14):SPEC.NO., s. 110-112
-
Tidskriftsartikel (refereegranskat)abstract
- Cartilage content of proteoglycans decreases early in induced degenerative hip joint disease. Remaining molecules show structural changes indicating fragmentation. Fragments lost from the articular cartilage are released to the synovial fluid, where they can be quantified by enzyme linked immunosorbent assay. Their amounts are related to the activity of the disease process.
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| 59. |
- Heinegård, Dick, et al.
(författare)
-
Connective tissue macromolecules as markers for tissue processes in joint disease.
- 1991
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Ingår i: European Journal of Rheumatology and Inflammation. - 0140-1610. ; 11:1, s. 91-99
-
Tidskriftsartikel (refereegranskat)abstract
- An early event in joint disease is a progressive destruction of the articular cartilage following degradation of matrix macromolecular constituents. The fragments thus formed are released into surrounding fluids by diffusion and can be detected and quantified by immunoassay. By using assays for macromolecules/fragments specific for cartilage, it is possible to monitor processes in a given articular cartilage. An example of such a molecule is the large aggregating proteoglycan, being a major constituent of cartilage. Fragmented proteoglycans are present at increased concentrations in synovial fluid of patients with early rheumatoid arthritis, reactive arthritis, crystal arthropathies and osteoarthritis. There are a number of other matrix proteins, where fragmentation and release is increased in joint disease. Since it is likely that the organisation of the cartilage is gradually destroyed in the degenerative process, it is likely that the pattern of fragments released varies with time. This can be verified by using a cartilage specific matrix protein, distinct from the proteoglycans. It may thus become possible to determine the prognosis of the disease process, the stage of the process and effects of therapy by the use of marker technology
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| 60. |
- Heinegård, Dick
(författare)
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From aggrecan to matrix
- 2009
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Ingår i: International Journal of Experimental Pathology. - 0959-9673. ; 90:2, s. 93-93
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Konferensbidrag (refereegranskat)
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