We have previously described the antifibrotic role of the soluble guanylate cyclase (sGC). The mode of action, however, remained elusive. In the present study, we describe a novel link between sGC ...signalling and transforming growth factor β (TGFβ) signalling that mediates the antifibrotic effects of the sGC.
Human fibroblasts and murine sGC knockout fibroblasts were treated with the sGC stimulator BAY 41-2272 or the stable cyclic guanosine monophosphate (cGMP) analogue 8-Bromo-cGMP and stimulated with TGFβ. sGC knockout fibroblasts were isolated from sGCI(fl/fl) mice, and recombination was induced by Cre-adenovirus. In vivo, we studied the antifibrotic effects of BAY 41-2272 in mice overexpressing a constitutively active TGF-β1 receptor.
sGC stimulation inhibited TGFβ-dependent fibroblast activation and collagen release. sGC knockout fibroblasts confirmed that the sGC is essential for the antifibrotic effects of BAY 41-2272. Furthermore, 8-Bromo-cGMP reduced TGFβ-dependent collagen release. While nuclear p-SMAD2 and 3 levels, SMAD reporter activity and transcription of classical TGFβ target genes remained unchanged, sGC stimulation blocked the phosphorylation of ERK. In vivo, sGC stimulation inhibited TGFβ-driven dermal fibrosis but did not change p-SMAD2 and 3 levels and TGFβ target gene expression, confirming that non-canonical TGFβ pathways mediate the antifibrotic sGC activity.
We elucidated the antifibrotic mode of action of the sGC that increases cGMP levels, blocks non-canonical TGFβ signalling and inhibits experimental fibrosis. Since sGC stimulators have shown excellent efficacy and tolerability in phase 3 clinical trials for pulmonary arterial hypertension, they may be further developed for the simultaneous treatment of fibrosis and vascular disease in systemic sclerosis.
Objective
To evaluate and characterize the appearance of articular cartilage in the tibiofemoral joint of young professional soccer players using T2-relaxation time evaluation on magnetic resonance ...imaging (MRI).
Design
In this study, we included 57 male adolescents from the youth academy of a professional soccer team. The MRI scans were acquired of the knee joint of the supporting leg. An “early unloading” (minute 0) and “late unloading” (minute 28) T2-sequence was included in the set of images. Quantitative T2-analysis was performed in the femorotibial joint cartilage in 4 slices with each 10 regions of interest (ROIs). Statistical evaluation, using Wilcoxon signed-rank tests, was primarily performed to compare the T2 values of the “early unloading” and “late unloading.”
Results
When comparing “early unloading” with “late unloading,” our findings showed a significant increase of T2-relaxation times in the weightbearing femoral cartilage of the medial (P < 0.001) and lateral (P < 0.001) compartment of the knee and in the tibial cartilage of the medial compartment (P < 0.001).
Conclusion
In this study, alterations of the cartilage were found with a maximum in the medial condyle where the biomechanical load of the knee joint is highest, as well as where most of the chronic cartilage lesions occur. To avoid chronic damage, special focus should be laid on this region.
Objectives
The purpose of this study was to assess morphological and quantitative changes of the anterior cruciate ligament (ACL) and cartilage after ACL repair.
Methods
7T MRI of the knee was ...acquired in 31 patients 1.5 years after ACL repair and in 13 controls. Proton density-weighted images with fat saturation (PD-fs) were acquired to assess ACL width, signal intensity, elongation, and fraying. T2/T2* mapping was performed for assessment of ACL and cartilage. Segmentation of the ACL, femoral, and tibial cartilage was carried out at 12 ROIs. The outcome evaluation consisted of the Lysholm Knee Score and International Knee Documentation Committee (IKDC) subjective score and clinical examination.
Results
ACL showed a normal signal intensity in 96.8% and an increased width in 76.5% after repair. Fraying occurred in 22.6% without having an impact on the clinical outcome (Lysholm score: 90.39 ± 9.75,
p
= 0.76 compared to controls). T2 analysis of the ACL revealed no difference between patients and controls (
p
= 0.74). Compared to controls, assessment of the femoral and tibial cartilage showed a significant increase of T2* times in all ROIs, except at the posterolateral femur. Patients presented a good outcome in clinical examination with a Lysholm score of 87.19 ± 14.89 and IKDC of 80.23 ± 16.84.
Conclusion
T2 mapping results suggest that the tissue composition of the ACL after repair is similar to that of a native ACL after surgery, whereas the ACL exhibits an increased width. Fraying of the ACL can occur without having any impact on functional outcomes. T2* analysis revealed early degradation at the cartilage.
Clinical relevance statement
MRI represents a noninvasive diagnostic tool for the morphological and compositional assessment of the anterior cruciate ligament after repair, whereas knowledge about post-surgical alterations is crucial for adequate imaging interpretation.
Key Points
• There has been renewed interest in repairing the anterior cruciate ligament with a proximally torn ligament.
• T2 times of the anterior cruciate ligament do not differ between anterior cruciate ligament repair patients and controls.
• T2 mapping may serve as a surrogate for the evaluation of the anterior cruciate ligament after repair.
Background
Patient education is crucial for successful chronic disease management. Current education material for rheumatic patients however rarely includes images of disease pathologies, limiting ...patients’ disease understanding. Cinematic rendering (CR) is a new tool that allows segmentation of standard medical images (DICOMs) into pictures that illustrate disease pathologies in a photorealistic way. Thus CR has the potential to simplify and improve the explanation of disease pathologies, disease activity and disease consequences and could therefore be a valuable tool to effectively educate and inform patients about their rheumatic and musculoskeletal disease (RMD).
Objectives
To examine the feasibility of creating photorealistic images using CR from RMD patients depicting typical rheumatic disease pathologies and, in a second step to investigate the patient-perceived educational potential of these photorealistic images in clinical routine.
Methods
We selected conventional, high-resolution (HR) and positron emission tomography (PET) computed tomography (CT) images of patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (axSpA), and giant cell arteritis (GCA) that showed typical respective disease pathologies. These images were segmented using CR technique. In a prospective study, physicians used CR-enhanced and conventional original images to explain the depicted pathognomonic pathologies to patients with the respective rheumatic disease. Patients were then asked to complete a questionnaire evaluating the perceived usefulness of being presented with CR-enhanced images to better understand their underlying disease.
Results
CR images were successfully generated from above mentioned CT methods. Pathologies such as bone erosions, bony spurs, bone loss, ankylosis, and PET-based inflammation could be visualized in photorealistic detail. A total of 79 patients (61% females) with rheumatic diseases (RA 29%, PsA 29%, axSpA 24%, GCA 18%) were interviewed and answered the quantitative questionnaire. Mean age was 55.4 ± 12.6 years. Irrespective of disease, all patients agreed or highly agreed that CR-based images help to improve disease understanding, should be shown at disease onset, provide a rationale to regularly take medication and would like to have access to their own CR-enhanced images.
Conclusion
Conventional disease images can successfully be turned into photorealistic disease depictions using CR. Patients perceived CR images as a valuable addition to current patient education, enabling personalized disease education and potentially increased medication adherence.
Purpose
The study aims to detect regions at risk for (pre-)osteoarthritis in the tibiofemoral joint of young professional soccer players by evaluating cartilage composition by T2 mapping in a 3 T ...magnetic resonance imaging setting.
Methods
In this longitudinal study, 20 professional adolescent soccer players were included. Tibiofemoral cartilage was assessed by quantitative T2 mapping and T2 values were evaluated by regions of interest analysis. Statistical evaluation, using Wilcoxon signed-rank tests, was performed to compare global T2 values and subregional T2 values between a baseline and a follow-up investigation 4.3 years later. Based on the average of playing time (15 years) we divided the cohort in 2 groups and differences were evaluated.
Results
When comparing baseline and follow-up, our findings showed statistically significant increases of the global medial tibial and femoral T2 values. The most noticeable results of the subregional T2 analysis were statistically significant increases in the medial posterior zones (deep femoral 36.1 vs. 39.5, P = 0.001; superficial femoral 57.0 vs. 62.4, P = 0.034; deep tibial 28.3 vs. 34.1, P = 0.009; superficial tibial 43.2 vs. 55.3, P = 0.002).
Conclusion
The elevation of T2 values in the medial, especially medial posterior, compartment of the knee joint indicates that these regions are at risk for early cartilage degeneration already at the time of adolescence. The findings can help individualize and optimize training concepts and to be aware of the chronic stress on these vulnerable areas. Prevention programs should be established in young players to avoid further cartilage damage.
(1) Background: To assess whether clinical outcomes correlate with tissue changes in the intervertebral discs (IVDs) after kyphoplasty as treatment for vertebral fractures, quantitative MRI was ...applied. (2) Methods: Quantitative T2 mapping acquired in a 3 T MRI scanner of the thoracolumbar spine was performed in 20 patients two years after kyphoplasty. The IVDs adjacent and nonadjacent to the treated vertebrae were divided into six regions of interest (ROI), which were further categorised into inner (ROI 2-5) and outer (ROI 1 and 6) parts of the IVDs, and the T2 values were analysed. T2 values of adjacent discs were correlated with the items of questionnaires evaluating the clinical outcome (i.e., 36-Item Short Form Survey). (3) Results: Lower T2 values in adjacent IVDs correlated with poorer physical outcome two years after kyphoplasty. The inner part of the IVDs adjacent to treated vertebrae showed statistically significant lower T2 values in segments L2/L3 and L3/L4 compared to nonadjacent ones. Patients with lower T2 values showed more pain and physical limitations in everyday life. (4) Conclusions: Quantitative T2 mapping can detect IVD degeneration in patients after kyphoplasty and correlates with the physical outcome. This technique could help to gain better insights into alterations in tissue composition following kyphoplasty and the consequences for the patients' quality of life.
The repair of large articular cartilage lesions is still a major challenge. In particular, the fixation of the grafts to the subchondral bone plate represents an unresolved problem. In this work, we ...present a completely novel concept based on a modular lattice, combining building blocks of different ceramic materials, anchoring pins and space for cell-loaded hydrogels or other scaffold materials. This concept targets not only circumscribed cartilage defects but also large osteoarthritic lesions. It spans the bridge between cell therapy and artificial joint arthroplasty, and thus is of significant medical and socioeconomic impact.
Die Behandlung von Verletzungen und Schäden des Gelenkknorpels ist ein wichtiges Gebiet in der Sportorthopädie. Die Bildgebung ist als Ergänzung zur Anamnese und der klinischen Untersuchung in der ...Diagnostik und im Therapiemonitoring der Gelenke unerlässlich geworden. Die wichtigste Methode in der Erkennung von Knorpelveränderungen und -schäden ist die Magnetresonanztomographie (MRT). Hoch aufgelöste morphologische und auch biochemische MRT Sequenzen ermöglichen mittlerweile die Darstellung sehr feiner Knorpelpathologien. Die morphologische Bildgebung ermöglicht die Beurteilung der Ausdehnung von Knorpelschäden und der angrenzenden Strukturen inklusive des darunter liegenden Knochens; hierfür haben sich verschiedene Scores etabliert. Auch in der postoperativen Darstellung nach Knorpeltherapie spielt sie eine wichtige Rolle. Die quantitative, kompositionelle Bildgebung zielt darauf ab, Veränderungen in der biochemischen Zusammensetzung des Knorpels zu erfassen und quantitative Werte zu entwickeln, die eine objektive Beurteilung der Gewebe-Güte ermöglichen.
The treatment of articular cartilage injuries and damage is an important topic in sports orthopedics. Imaging has become essential as a complement to history and clinical examination in joint diagnosis and therapy monitoring. Magnetic Resonance Imaging (MRI) has become indispensable for the assessment of cartilage and cartilage damage. High-resolution morphologic and also biochemical MRI sequences now allow visualization of very fine cartilage pathologies. Morphologic imaging allows assessment of the extent of cartilage damage and adjacent structures, including the underlying bone; various scores have become established for this purpose. It also plays an important role in postoperative imaging after cartilage therapy. Compositional quantitative imaging aims to detect changes in the biochemical composition of cartilage and to develop quantitative values that allow objective assessment of tissue quality.
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