| 1. |
- Ali, Neserin, et al.
(author)
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Proteomics profiling of human synovial fluid suggests increased protein interplay in early-osteoarthritis (OA) that is lost in late-stage OA
- 2022
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In: Molecular & Cellular Proteomics. - : Elsevier BV. - 1535-9484 .- 1535-9476.
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Journal article (peer-reviewed)abstract
- The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from deceased controls without knee OA.Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group.More proteins were increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time this study illustrated distinct patterns in protein co-expression suggesting that the interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should focus on earlier stages of the disease than previously considered.
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| 2. |
- Dell'Isola, Andrea, et al.
(author)
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Risk of Comorbidities Following Physician-Diagnosed Knee or Hip Osteoarthritis : A Register-Based Cohort Study
- 2022
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In: Arthritis Care and Research. - : Wiley. - 2151-464X .- 2151-4658. ; 74:10, s. 1689-1695
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Journal article (peer-reviewed)abstract
- Objective: To estimate the risk of developing comorbidities in patients after physician-diagnosed knee or hip osteoarthritis (OA). Methods: This was a cohort study using Swedish longitudinal health care register data; we studied residents in the Skåne region age ≥35 years on January 1, 2010 who were free from diagnosed hip or knee OA (n = 548,681). We then identified subjects with at least 1 new diagnosis of knee or hip OA (incident OA) between 2010 and 2017 (n = 50,942 considered exposed). Subjects without diagnosed OA were considered unexposed. From January 2010 both unexposed and exposed subjects were observed for the occurrence of 18 different predefined comorbidities until either relocation outside of the region, death, occurrence of the comorbidity, or December 2017, whichever came first. We calculated unadjusted hazard ratios (HRs) and adjusted HRs of comorbidities using Cox models with knee and hip OA as time-varying exposures. Results: Subjects with incident knee or hip OA had 7% to 60% higher adjusted HRs (range 1.07–1.60) of depression, cardiovascular diseases, back pain, and osteoporosis than individuals without an OA diagnosis. An increased risk of diabetes mellitus was found only for knee OA (adjusted HR 1.19 [95% confidence interval 1.13–1.26]). For the rest of the diagnoses, we found either no increased risk or estimates with wide confidence intervals, excluding clear interpretations of the direction or size of effects. Conclusion: Incident physician-diagnosed knee and hip OA is associated with an increased risk of depression, cardiovascular diseases, back pain, osteoporosis, and diabetes mellitus. However, the latter was only found for knee OA.
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| 3. |
- Dell'Isola, Andrea, et al.
(author)
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The impact of first and second wave of COVID-19 on knee and hip surgeries in Sweden
- 2021
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In: Journal of Experimental Orthopaedics. - : Springer Science and Business Media LLC. - 2197-1153. ; 8
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Journal article (peer-reviewed)abstract
- PURPOSE: To investigate the impact of COVID-19 in Sweden on rates of knee and hip surgeries.METHODS: We used healthcare data for the population of the southernmost region in Sweden (1.4 million inhabitants). We did an interrupted time-series analysis to estimate changes in rates and trends of joint replacements (JR), arthroscopies, and fracture surgeries for knee or hip in April-December 2020 compared to pre-COVID-19 levels adjusting for seasonal variations.RESULTS: We found a drop of 54% (95% CI 42%; 68%) and 42% (95% CI 32%; 52%), respectively, in the rate of JRs and arthroscopies in April 2020 when compared to the counterfactual scenario. This was followed by an increase that brought the rates of JRs and arthroscopies back to their predicted levels also during the beginning of the second wave (November-December 2020). Acute fracture surgeries were largely unaffected, i.e. did not show any decrease as observed for the other surgeries.CONCLUSIONS: In southern Sweden, we observed a marked decrease in elective knee and hip surgeries following the first wave of Covid-19. The rates remained close to normal during the beginning of the second wave suggesting that important elective surgeries for patients with end-stage osteoarthritis can still be offered despite an ongoing pandemic provided adequate routines and hospital resources.
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| 4. |
- Einarsson, Emma, et al.
(author)
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Relating MR relaxation times of ex vivo meniscus to tissue degeneration through comparison with histopathology
- 2020
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In: Osteoarthritis and Cartilage Open. - : Elsevier BV. - 2665-9131. ; 2:2
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Journal article (peer-reviewed)abstract
- Background: Quantitative magnetic resonance imaging (MRI), e.g. relaxation parameter mapping, may be sensitive to structural and compositional tissue changes, and could potentially be used to non-invasively detect and monitor early meniscus degeneration related to knee osteoarthritis. Objective: To investigate MR relaxation times as potential biomarkers for meniscus degeneration through comparisons with histopathology. Methods: We measured MR relaxation parameters in the posterior horn of 40 menisci (medial and lateral) at a wide range of degenerative stages. T1, T2 and T2∗ were mapped using standard and ultrashort echo time sequences at 9.4 T and compared to gold standard histology using Pauli's histopathological scoring system, including assessment of surface integrity, collagen organization, cellularity and Safranin-O staining. Results: All three relaxation times increased with total Pauli score (mean difference per score (95% CI) for T2∗: 0.62 (0.37, 0.86), T2: 0.83 (0.53, 1.1) and T1: 24.7 (16.5, 32.8) ms/score). Clear associations were seen with scores of surface integrity (mean difference per score for T2∗: 3.0 (1.8, 4.2), T2: 4.0 (2.5, 5.5) and T1: 116 (75.6, 156) ms/score) and collagen organization (mean difference between highest and lowest score for T2∗: 5.3 (1.6, 8.9), T2: 6.1 (1.7, 11) and T1: 204 (75.9, 332) ms). The results were less clear for the remaining histopathological measures. Conclusions: MR relaxation times T1, T2 and T2∗ of ex vivo human menisci are associated with histologically verified degenerative processes, in particular related to surface integrity and collagen organization. If confirmed in vivo, MR relaxation times may thus be potential biomarkers for meniscus degeneration.
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| 5. |
- Finnilä, Mikko A J, et al.
(author)
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Mineral Crystal Thickness in Calcified Cartilage and Subchondral Bone in Healthy and Osteoarthritic Human Knees
- 2022
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In: Journal of Bone and Mineral Research. - : Wiley. - 1523-4681 .- 0884-0431. ; 37:9, s. 1700-1710
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Journal article (peer-reviewed)abstract
- Osteoarthritis (OA) is the most common joint disease, where articular cartilage degradation is often accompanied with sclerosis of the subchondral bone. However, the association between OA and tissue mineralization at the nanostructural level is currently not understood. In particular, it is technically challenging to study calcified cartilage, where relevant but poorly understood pathological processes such as tidemark multiplication and advancement occur. Here, we used state-of-the-art microfocus small-angle X-ray scattering with a 5-μm spatial resolution to determine the size and organization of the mineral crystals at the nanostructural level in human subchondral bone and calcified cartilage. Specimens with a wide spectrum of OA severities were acquired from both medial and lateral compartments of medial compartment knee OA patients (n = 15) and cadaver knees (n = 10). Opposing the common notion, we found that calcified cartilage has thicker and more mutually aligned mineral crystals than adjoining bone. In addition, we, for the first time, identified a well-defined layer of calcified cartilage associated with pathological tidemark multiplication, containing 0.32 nm thicker crystals compared to the rest of calcified cartilage. Finally, we found 0.2 nm thicker mineral crystals in both tissues of the lateral compartment in OA compared with healthy knees, indicating a loading-related disease process because the lateral compartment is typically less loaded in medial compartment knee OA. In summary, we report novel changes in mineral crystal thickness during OA. Our data suggest that unloading in the knee might be involved with the growth of mineral crystals, which is especially evident in the calcified cartilage.
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| 6. |
- Folkesson, Elin, et al.
(author)
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Proteomic characterization of the normal human medial meniscus body using data-independent acquisition mass spectrometry
- 2020
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In: Journal of Orthopaedic Research. - : Wiley. - 0736-0266 .- 1554-527X. ; 38:8, s. 1735-1745
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Journal article (peer-reviewed)abstract
- Recent research suggests an important role of the meniscus in the development of knee osteoarthritis. We, therefore, aimed to analyze the proteome of the normal human meniscus body, and specifically to gain new knowledge on global protein expression in the different radial zones. Medial menisci were retrieved from the right knees of 10 human cadaveric donors, from which we cut a 2 mm radial slice from the mid-portion of the meniscal body. This slice was further divided into three zones: inner, middle, and peripheral. Proteins were extracted and prepared for mass spectrometric analysis using data-independent acquisition. We performed subsequent data searches using Spectronaut Pulsar and used fixed-effect linear regression models for statistical analysis. We identified 638 proteins and after statistical analysis, we observed the greatest number of differentially expressed proteins between the inner and peripheral zones (163 proteins) and the peripheral and middle zones (136 proteins), with myocilin being the protein with the largest fold-change in both comparisons. Chondroadherin was one of eight proteins that differed between the inner and middle zones. Functional enrichment analyses showed that the peripheral one-third of the medial meniscus body differed substantially from the two more centrally located zones, which were more similar to each other. This is probably related to the higher content of cells and vascularization in the peripheral zone, whereas the middle and inner zones of the meniscal body appear to be more similar to hyaline cartilage, with high levels of extracellular matrix proteins such as aggrecan and collagen type II.
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| 7. |
- Kuru, Erkin, et al.
(author)
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In Situ probing of newly synthesized peptidoglycan in live bacteria with fluorescent D-amino acids
- 2012
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In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851 .- 1521-3773. ; 51:50, s. 12519-12523
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Journal article (peer-reviewed)abstract
- Tracking a bug's life: Peptidoglycan (PG) of diverse bacteria is labeled by exploiting the tolerance of cells for incorporating different non-natural D-amino acids. These nontoxic D-amino acids preferably label the sites of active PG synthesis, thereby enabling fine spatiotemporal tracking of cell-wall dynamics in phylogenetically and morphologically diverse bacteria. HCC = 7-hydroxycoumarin, NBD = 7-nitrobenzofurazan, TAMRA = carboxytetramethylrhodamine.
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| 8. |
- Magnusson, Karin, et al.
(author)
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High genetic contribution to anterior cruciate ligament rupture : Heritability ∼69%
- 2020
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In: British journal of sports medicine. - : BMJ. - 0306-3674 .- 1473-0480.
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Journal article (peer-reviewed)abstract
- Objectives: We aimed to determine the lifetime genetic risk for anterior cruciate ligament (ACL) rupture. Methods: We used a twin study approach, linking the Swedish Twin Register with national healthcare data to form a 30 year, population wide, longitudinal twin cohort. We studied ACL rupture in this cohort of 88 414 identical and fraternal twin pairs, aged ≥17 years, to determine the familial risk and heritability of ACL rupture. Results: The incidence rate of ACL rupture was 70 (95% CI 66 to 74) per 100 000 person years. The familial risk, which is the excess risk ratio (RR) of the second twin having ACL rupture given that the first twin has had such a rupture, was higher in identical twin pairs (RR=8.6, 95% CI 6.2 to 11.0) than in fraternal twin pairs (RR=1.9, 95% CI 0.9 to 3.0). The overall heritability of ACL rupture was high, 69% (95% CI 47 to 91), increasing from 60% at age 17 years to 80% at age 60 years. Women and men had similar familial risk and heritability of ACL rupture. Conclusion: The genetic contribution to ACL rupture of ∼69% is high and suggests strong familial clustering. If clinicians recognise the high genetic risk of such injury, they may be better able to counsel athletes whose near relatives have had ACL rupture.
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