| 1. |
- Demetris, Anthony J, et al.
(författare)
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Liver biopsy interpretation for causes of late liver allograft dysfunction.
- 2006
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Ingår i: Hepatology (Baltimore, Md.). - : Ovid Technologies (Wolters Kluwer Health). - 0270-9139 .- 1527-3350. ; 44:2, s. 489-501
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Tidskriftsartikel (refereegranskat)abstract
- Evaluation of needle biopsies and extensive clinicopathological correlation play an important role in the determination of liver allograft dysfunction occurring more than 1 year after transplantation. Interpretation of these biopsies can be quite difficult because of the high incidence of recurrent diseases that show histopathological, clinical, and serological features that overlap with each other and with rejection. Also, more than one insult can contribute to allograft injury. In an attempt to enable centers to compare and pool results, improve therapy, and better understand pathophysiological disease mechanisms, the Banff Working Group on Liver Allograft Pathology herein proposes a set of consensus criteria for the most common and problematic causes of late liver allograft dysfunction, including late-onset acute and chronic rejection, recurrent and new-onset viral and autoimmune hepatitis, biliary strictures, and recurrent primary biliary cirrhosis and primary sclerosing cholangitis. A discussion of differential diagnosis is also presented.
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| 2. |
- Franzén, Ahnders, et al.
(författare)
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Altered osteoclast development and function in osteopontin deficient mice.
- 2008
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Ingår i: Journal of Orthopaedic Research. - : Wiley. - 1554-527X .- 0736-0266. ; 26:5, s. 721-728
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Tidskriftsartikel (refereegranskat)abstract
- The role of osteopontin in bone resorption was elucidated by studies of mice with knock out of the osteopontin gene generated by a different approach compared to previous models. Thus, a targeting vector with the promoter region as well as exons 1, 2, and 3 of the osteopontin gene was replaced by a loxP-flanked Neo-TK cassette, and this cassette was eliminated through transient expression of Cre recombinase. The recombined ES cells were used to create mice lacking expression of the osteopontin gene. Tissues from these mice were subjected structural and molecular analyses including morphometry and proteomics. The bone of the null mice contained no osteopontin but showed no significant alterations with regard to other bone proteins. The bone volume was normal in young null animals but in the lower metaphysis, the volume and number of osteoclasts were increased. Notably, the volume and length of the osteoclast ruffled border was several folds lower, indicating a lower resorptive capacity. The null mice did not develop the bone loss characteristic for osteoporosis demonstrated in old wild-type female animals. This quantitative study demonstrates a bone phenotype in the osteopontin null mice of all ages. The data provides further evidence for a role of osteopontin in osteoclast activity. (c) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
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| 3. |
- Hessle, Lovisa, et al.
(författare)
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The skeletal phenotype of chondroadherin deficient mice.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their α2β1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3-6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the α1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth.
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| 4. |
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| 5. |
- Muller, Catharina, et al.
(författare)
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Quantitative proteomics at different depths in human articular cartilage reveals unique patterns of protein distribution.
- 2014
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Ingår i: Matrix Biology. - : Elsevier BV. - 1569-1802 .- 0945-053X. ; 40:Sep 1, s. 34-45
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Tidskriftsartikel (refereegranskat)abstract
- The articular cartilage of synovial joints ensures friction-free mobility and attenuates mechanical impact on the joint during movement. These functions are mediated by the complex network of extracellular molecules characteristic for articular cartilage. Zonal differences in the extracellular matrix (ECM) are well recognized. However, knowledge about the precise molecular composition in the different zones remains limited. In the present study, we investigated the distribution of ECM molecules along the surface-to-bone axis, using quantitative non-targeted as well as targeted proteomics.\ In a discovery approach, iTRAQ mass spectrometry was used to identify all extractable ECM proteins in the different layers of a human lateral tibial plateau full thickness cartilage sample. A targeted MRM mass spectrometry approach was then applied to verify these findings and to extend the analysis to four medial tibial plateau samples. In the lateral tibial plateau sample, the unique distribution patterns of 70 ECM proteins were identified, revealing groups of proteins with a preferential distribution to the superficial, intermediate or deep regions of articular cartilage. The detailed analysis of selected 29 proteins confirmed these findings and revealed similar distribution patterns in the four medial tibial plateau samples. The results of this study allow, for the first time, an overview of the zonal distribution of a broad range of cartilage ECM proteins and open up further investigations of the functional roles of matrix proteins in the different zones of articular cartilage in health and disease.
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| 6. |
- Svensson, Liz, et al.
(författare)
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Cartilage oligomeric matrix protein-deficient mice have normal skeletal development.
- 2002
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Ingår i: Molecular and Cellular Biology. - 0270-7306. ; 22:12, s. 4366-4371
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Tidskriftsartikel (refereegranskat)abstract
- Cartilage oligomeric matrix protein (COMP) belongs to the thrombospondin family and is a homopentamer primarily expressed in cartilage. Mutations in the COMP gene result in the autosomal dominant chondrodysplasias pseudoachondroplasia (PSACH) and some types of multiple epiphyseal dysplasia (MED), which are characterized by mild to severe short-limb dwarfism and early-onset osteoarthritis. We have generated COMP-null mice to study the role of COMP in vivo. These mice show no anatomical, histological, or ultrastructural abnormalities and show none of the clinical signs of PSACH or MED. Northern blot analysis and immunohistochemical analysis of cartilage indicate that the lack of COMP is not compensated for by any other member of the thrombospondin family. The results also show that the phenotype in PSACH/MED cartilage disorders is not caused by the reduced amount of COMP.
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| 7. |
- Önnerfjord, Patrik, et al.
(författare)
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Quantitative proteomic analysis of eight cartilaginous tissues reveals characteristic differences as well as similarities between subgroups
- 2012
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 287:23, s. 18913-18924
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Tidskriftsartikel (refereegranskat)abstract
- Human synovial joints display a characteristic anatomic distribution of arthritis, e.g. rheumatoid arthritis primarily affects the metacarpophalangeal and proximal finger joints, but rarely the distal finger joints, whereas osteoarthritis occurs in the distal and proximal finger joints. Pelvospondylitis has a selective localization to the spine and sacroiliac joints. Is this tropism due to differences between the cartilages at the molecular level? To substantiate this concept the present study provides a background detailed compositional analysis by relative quantification of extracellular matrix proteins in articular cartilages, meniscus, intervertebral disc, rib, and tracheal cartilages on samples from 5-6 different individuals using an optimized approach for proteomics. Tissue extraction followed by trypsin digestion and two-dimensional LC separations coupled to tandem mass spectrometry, relative quantification with isobaric labeling, iTRAQ (TM), was used to compare the relative abundance of about 150 proteins. There were clear differences in protein patterns between different kinds of cartilages. Matrilin-1 and epiphycan were specific for rib and trachea, whereas asporin was particularly abundant in the meniscus. Interestingly, lubricin was prominent in the intervertebral disc, especially in the nucleus pulposus. Fibromodulin and lumican showed distributions that were mirror images of one other. Analyses of the insoluble residues from guanidine extraction revealed that a fraction of several proteins remained unextracted, e.g. asporin, CILP, and COMP, indicating cross-linking. Distinct differences in protein patterns may relate to different tissue mechanical properties, and to the intriguing tropism in different patterns of joint pathology.
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