Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA161499 | ENA |
REPOSITORIES: ENA
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Project description:Inflammatory arthritis is associated with bone loss and fractures due to abnormal bone remodelling. Bone remodelling is 'uncoupled' with bone resorption increased and bone formation suppressed. These changes resemble those seen in patients treated with therapeutic glucocorticoids, and in both of these situations, altered wnt signalling is implicated. Recent studies have highlighted the importance of the synovial fibroblast in mediating abnormal bone remodelling during inflammation. The wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation, and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Here we show that DKK1 expression by primary human synovial fibroblasts is more potently regulated by glucocorticoids than pro-inflammatory cytokines. Glucocorticoids, but not TNF-alpha, regulated expression of multiple wnt agonists and antagonists in favour of inhibition of wnt signalling. In vitro TNF-alpha and IL1-beta indirectly regulate DKK1 production through increased expression of the glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These results demonstrate that the links between synovial inflammation, altered wnt signalling and bone remodelling may not be direct but are dependent on local activation of endogenous glucocorticoids. Human fibroblast-like synoviocytes isolated from patients with rheumatoid arthritis treated with either vehicle, TNF or dexamethasone (dex). Gene arrays for control, TNF and dexamethasone treatments were performed on three separate synovial fibroblast cell lines isolated from three rheumatoid arthritis patients. All fold changes displayed are the combined results of the three separate fibroblast lines.
2012-04-24 | E-GEOD-37520 | biostudies-arrayexpress
Project description:Inflammatory arthritis is associated with bone loss and fractures due to abnormal bone remodelling. Bone remodelling is 'uncoupled' with bone resorption increased and bone formation suppressed. These changes resemble those seen in patients treated with therapeutic glucocorticoids, and in both of these situations, altered wnt signalling is implicated. Recent studies have highlighted the importance of the synovial fibroblast in mediating abnormal bone remodelling during inflammation. The wnt antagonist dickkopf-1 (DKK1) is secreted by synovial fibroblasts in response to inflammation, and this protein has been proposed to be a master regulator of bone remodelling in inflammatory arthritis. Here we show that DKK1 expression by primary human synovial fibroblasts is more potently regulated by glucocorticoids than pro-inflammatory cytokines. Glucocorticoids, but not TNF-alpha, regulated expression of multiple wnt agonists and antagonists in favour of inhibition of wnt signalling. In vitro TNF-alpha and IL1-beta indirectly regulate DKK1 production through increased expression of the glucocorticoid activating enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). These results demonstrate that the links between synovial inflammation, altered wnt signalling and bone remodelling may not be direct but are dependent on local activation of endogenous glucocorticoids.
2012-04-24 | GSE37520 | GEO
Project description:The study presents: - an optimized synovium dissociation protocol for single cell RNA-sequencing studies of the human synovium. The protocol enables the isolation of high yield of viable synovial cells from prospectively collected fresh synovial biopsies from patients with inflammatory arthritis with a minimal sample droupout. The protocol is derived from the method for dissociation of cryopreserved synovia published by Donlin and colleagues (Arthritis Res. Ther. 2019). - a reference single-cell atlas of fresh human synovium in inflammatory arthritis, comprising more than 100´000 unsorted synovial scRNA-seq profiles from 27 freshly dissociated synovia of patients with different types of inflammatory arthritis. The synovial cells segregate into ten lymphoid, 14 myeloid and 17 stromal synovial cell populations and subpopulations, including synovial neutrophils, representing broadly representing the cellular heterogeneity and composition of the human synovium in inflammatory arthritis.
2024-04-21 | E-MTAB-11791 | biostudies-arrayexpress
Project description:Rehabilitation using cryotherapy has widely been used in inflammatory diseases to relieve pain and decrease the disease activity. The aim of this study was to explore the metabolite changes in inflammatory knee-joint synovial fluids following local cryotherapy treatment (ice or cold CO2). We used proton nuclear magnetic resonance (1H NMR) spectroscopy to assess the metabolite patterns in synovial fluid (SF) in patients with knee arthritis (n = 46) before (D0) and after (D1, 24 h later) two applications of local cryotherapy. Spectra from aqueous samples and organic extracts were obtained with an 11.75 Tesla spectrometer. The metabolite concentrations within the SF were compared between D1 and D0 using multiple comparisons with the application of a false discovery rate (FDR) adjusted at 10% for each metabolite. A total of 32 metabolites/chemical structures were identified including amino acids, organic acids, fatty acids or sugars. Pyruvate, alanine, citrate, threonine was significantly higher at D1 vs D0 (p < 0.05). Tyrosine concentration significantly decreases after cryotherapy application (p < 0.001). We did not observe any effect of gender and cooling technique on metabolite concentrations between D0 and D1 (p > 0.05). The present study provides new insight into a short-term effect of cold stimulus in synovial fluid from patients with knee arthritis. Our observations suggest that the increased level of metabolites involved in energy metabolism may explain the underlying molecular pathways that mediate the antioxidant and anti-inflammatory capacities of cryotherapy.
2020-11-10 | MTBLS1894 | MetaboLights
Project description:We sequenced (bulk RNA-seq) conventional (c)DC1, cDC2 and monocytes from a local inflammatory site, namely synovial fluid (SF) from patients suffering from a chronic inflammatory condition, Juvenile Idiopathic Arthritis (JIA). To be able to compare to steady state, we also sequenced cDC2 and monocyte subsets from peripheral blood of healthy controls.
2023-01-13 | GSE220264 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Here we explored how the human macrophage response to tumor necrosis factor (TNF) is regulated by human synovial fibroblasts, the representative stromal cell type in the synovial lining of joints that become activated during inflammatory arthritis. Genome-wide transcriptome analysis (RNAseq) showed that co-cultured synovial fibroblasts modulate the expression of approximately one third of TNF-inducible genes in macrophages, including expression of target genes in pathways important for macrophage survival and polarization towards an alternatively activated phenotype. This work furthers our understanding of the interplay between innate immune and stromal cells during an inflammatory response, one that is particularly relevant to inflammatory arthritis. Our findings also identify modulation of macrophage phenotype as a new function for synovial fibroblasts that may prove to be a contributing factor in arthritis pathogenesis.
2014-08-04 | GSE57723 | GEO
Project description:Transcriptional profiling of Homo sapiens inflammatory skin diseases (whole skin biospies): Psoriasis (Pso), vs Atopic Dermatitis (AD) vs Lichen planus (Li), vs Contact Eczema (KE), vs Healthy control (KO) In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation. In recent years, different genes and proteins have been highlighted as potential biomarkers for psoriasis, one of the most common inflammatory skin diseases worldwide. However, most of these markers are not psoriasis-specific but also found in other inflammatory disorders. We performed an unsupervised cluster analysis of gene expression profiles in 150 psoriasis patients and other inflammatory skin diseases (atopic dermatitis, lichen planus, contact eczema, and healthy controls). We identified a cluster of IL-17/TNFα-associated genes specifically expressed in psoriasis, among which IL-36γ was the most outstanding marker. In subsequent immunohistological analyses IL-36γ was confirmed to be expressed in psoriasis lesions only. IL-36γ peripheral blood serum levels were found to be closely associated with disease activity, and they decreased after anti-TNFα-treatment. Furthermore, IL-36γ immunohistochemistry was found to be a helpful marker in the histological differential diagnosis between psoriasis and eczema in diagnostically challenging cases. These features highlight IL-36γ as a valuable biomarker in psoriasis patients, both for diagnostic purposes and measurement of disease activity during the clinical course. Furthermore, IL-36γ might also provide a future drug target, due to its potential amplifier role in TNFα- and IL-17 pathways in psoriatic skin inflammation.
2014-12-02 | GSE63741 | GEO
Project description:Mast cells are phenotypically and functionally highly heterogeneous, and their state is possibly controlled by their local microenvironment. Therefore, concrete analyses are needed to understand whether mast cells act as powerful motivators or dispensable bystanders in specific diseases. Here, we evaluated the correlation between synovial mast cells and rheumatoid arthritis (RA) disease severity, and the efficacy of therapeutic interventions against mast cells. We showed that degranulation of mast cells in inflammatory synovial tissues of RA patients was induced via MAS-related G protein-coupled receptor X2 (MRGPRX2), and the expression of MHC class II (MHC II) and costimulatory molecules on mast cells were upregulated. These unique signaling response led to mast cell activation and promoted T cell responses, resulting in the progression of RA. Collagen-induced arthritis mouse models treated with a combination of anti-IL-17A and cromolyn sodium, a mast cell membrane stabilizer, showed significantly reduced clinical severity and decreased bone erosion. The findings of the present study suggest that synovial microenvironment-influenced mast cells contribute to RA and may provide a novel mast cell-targeting therapy for RA.
2024-01-07 | PXD038584 | Pride
Project description:Gene expression in rheumatoid arthritis synovial macrophages
| PRJNA107955 | ENA