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- Folkesson, E., et al.
(författare)
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Proteomic comparison of osteoarthritic and reference human menisci using data-independent acquisition mass spectrometry
- 2020
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 28:8, s. 1092-1101
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Recent research in knee osteoarthritis (OA) highlights the role of the meniscus in OA pathology. Our aim was to compare the proteomes of medial and lateral menisci from end-stage medial compartment knee OA patients, with reference menisci from knee-healthy deceased donors, using mass spectrometry. Design: Tissue plugs of Ø3 mm were obtained from the posterior horns of the lateral and medial menisci from one knee of 10 knee-healthy deceased donors and 10 patients undergoing knee replacement. Proteins were extracted and prepared for mass spectrometric analysis. Statistical analysis was conducted on abundance data that was log2-transformed, using a linear mixed effects model and evaluated using pathway analysis. Results: We identified a total of 835 proteins in all samples, of which 331 were included in the statistical analysis. The largest differences could be seen between the medial menisci from OA patients and references, with most proteins showing higher intensities in the medial menisci from OA patients. Several matrix proteins, e.g., matrix metalloproteinase 3 (MMP3) (4.3 times higher values [95%CI 1.8, 10.6]), TIMP1 (3.5 [1.4, 8.5]), asporin (4.1 [1.7, 10.0]) and versican (4.4 [1.8, 10.9]), all showed higher abundance in medial menisci from OA patients compared to medial reference menisci. OA medial menisci also showed increased activation of several pathways involved in inflammation. Conclusion: An increase in protein abundance for proteins such as MMP and TIMP1 in the medial menisci from OA patients suggests simultaneous activation of both catabolic and anabolic processes that warrants further attention.
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- Karjalainen, V. P., et al.
(författare)
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Quantitative three-dimensional collagen orientation analysis of human meniscus posterior horn in health and osteoarthritis using micro-computed tomography
- 2021
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Ingår i: Osteoarthritis and Cartilage. - : Elsevier BV. - 1063-4584. ; 29:5, s. 762-772
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Knee osteoarthritis (OA) is associated with meniscal degeneration that may involve disorganization of the meniscal collagen fiber network. Our aims were to quantitatively analyze the microstructural organization of human meniscus samples in 3D using micro-computed tomography (μCT), and to compare the local microstructural organization between OA and donor samples. Method: We collected posterior horns of both medial and lateral human menisci from 10 end-stage medial compartment knee OA patients undergoing total knee replacement (medial & lateral OA) and 10 deceased donors without knee OA (medial & lateral donor). Posterior horns were dissected and fixed in formalin, dehydrated in ascending ethanol concentrations, treated with hexamethyldisilazane (HMDS), and imaged with μCT. We performed local orientation analysis of collagenous microstructure in 3D by calculating structure tensors from greyscale gradients within selected integration window to determine the polar angle for each voxel. Results: In donor samples, meniscus bundles were aligned circumferentially around the inner border of meniscus. In medial OA menisci, the organized structure of collagen network was lost, and main orientation was shifted away from the circumferential alignment. Quantitatively, medial OA menisci had the lowest mean orientation angle compared to all groups, −24° (95%CI -31 to −18) vs medial donor and −25° (95%CI -34 to −15) vs lateral OA. Conclusions: HMDS-based μCT imaging enabled quantitative analysis of meniscal collagen fiber bundles and their orientations in 3D. In human medial OA menisci, the collagen disorganization was profound with overall lower orientation angles, suggesting collagenous microstructure disorganization as an important part of meniscus degradation.
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