| 1. |
- Bjärdahlen, Anette
(författare)
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Extracellular Matrix Remodelling-Proteoglycan and collagen turnover in arthritis
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Rheumatoid arthritis is a chronic, inflammatory and systemic disease characterised by joint destruction and pannus formation. To enlarge the understanding how pannus and granulation tissue are formed two animal models were used; one using cartilage wrapped in cotton and implanted into a rat air pouch (AP) and one where mBSA induced arthritis (AIA) was performed. Cell cultures from synovial specimens were established and their significance in matrix production was evaluated. In the AP model the development new tissue was studied whereas in the AIA model remodelling of existing tissue occurred. In both animal models the cartilage undergoes destruction and thereby releases aggrecan. In the AIA model the cartilage remodelled over time. Here an increased amount of biglycan was seen early which was followed by an increased amount of collagen and decorin. This lead to a more fibrous cartilage with changed properties. When the cartilage was removed from its original place and implanted into the air pouch this phenomenon was not seen. Instead, a stable level of collagen was noted throughout the study and only 20% aggrecan remained. In pannus and in cotton, the same type of changes occurred. Versican and aggrecan were the first proteoglycans to appear in the tissue, thereafter an increase in the level of biglycan at the peek of inflammation. Also the trisomic cultures started producing versican, which was 4-fold elevated compared to the disomic cultures. Aggrecan leaking out of the degrading cartilage affects the development of the surrounding ECM, by sustaining the inflammation and thereby delaying the ECM formation. At later stages of the arthritis, elevated levels of collagen and decorin occurred. The increase in collagen correlated with the appearance of myofibroblasts. All these findings indicate an intricate interplay between cartilage and its surrounding.
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| 2. |
- Bjärdahlen, Anette, et al.
(författare)
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Myofibroblast accumulation correlates with the formation of fibrotic tissue in a rat air pouch model.
- 2002
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Ingår i: Journal of Rheumatology. - 0315-162X. ; 29:8, s. 1698-1707
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The pathogenesis of arthritic joints involves cartilage degradation and pannus formation. It is well known that pannus influences the cartilage; however, the mechanism behind how the degrading cartilage interacts with pannus is not well known. To investigate this interplay, the expression of extracellular matrix (ECM) components in pannus and the degrading cartilage was analyzed. METHODS: Studies were performed using a rat air pouch model where cotton with viable or killed cartilage was implanted into 7-day-old pouches for 1-28 days. The remodeling of cartilage and the formation of tissue in the cotton was characterized histologically by quantitation of infiltrated cells. The amounts of collagen, hyaluronan, and proteoglycan were estimated. RESULTS: Implantation of homologous femoral head cartilage in cotton resulted in extensive remodeling of cartilage and formation of ECM in the cotton. In cotton without cartilage, fibroblasts and myofibroblasts were the predominant cells in the early stage of analyses. The ECM formed in cotton was of a fibrotic type, with mainly collagen and smaller amounts of proteoglycans correlating to the presence of myofibroblasts. In the cotton with cartilage, however, inflammatory cells such as neutrophils, macrophages, and lymphocytes dominated. Delayed accumulation of collagen and increased synthesis of proteoglycans occurred early in cotton with viable as well as non-viable cartilage. In later stages, the cell pattern changed and the myofibroblasts emerged together with an increasing collagen formation. CONCLUSION: The interaction between cartilage and the newly formed granulation tissue results in a faster degradation of cartilage molecules, which in turn leak into the surrounding ECM and affect the recruitment of myofibroblasts. This indicates the importance of the micromatrix.
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| 3. |
- Eklund, Erik, et al.
(författare)
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Proteoglycan production in disomic and trisomy 7-carrying human synovial cells.
- 2002
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Ingår i: Matrix Biology. - 1569-1802. ; 21:4, s. 325-335
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Tidskriftsartikel (refereegranskat)abstract
- To gain further insight into the synthesis and structure of the synovial matrix of joints, we have established cell cultures from synovial specimens and elaborated their production of hyaluronan and proteoglycans. The cultures secreted mainly the small proteoglycan decorin, but also considerable amounts of the related biglycan and the large proteoglycan versican. Only minor amounts of heparan sulfate proteoglycans were found. All cultures also had a high production of hyaluronan, which highlights the important role for normal joint function of these cells. In joint diseases, a common feature is the presence of an extra chromosome 7 (trisomy 7) in the synovial cells. To study the possible consequences of trisomy 7 on the synovial cell function, we extended our study to cultures that had been sub-cloned to contain high amounts of trisomy 7-carrying cells. These cell cultures had approximately four times more versican than their disomic counterparts in the cell culture medium, indicating that versican may be a mediator in the processes of joint destructive disorders. To find an explanation for this increase in versican, we investigated the expression/secretion of PDGF-AA and IL-6, cytokines with their genes located to chromosome 7. Indeed, both these cytokines were increased in the cultures with high frequencies of trisomy 7. We then added the two cytokines to cell cultures of disomic synovial cells, but only cells treated with IL-6 displayed an increased amount of versican. Thus, we suggest that the increased amount of versican in cultures of trisomy 7-carrying cells relates to an autocrine loop involving an increased IL-6 production.
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