Metabolism in synovial macrophages are reprogrammed by synovial fibroblasts under inflammatory condition
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ABSTRACT:
PROVIDER: PRJNA597752 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10768574_1.fastq.gz | Fastqsanger.gz | |||
| SRR10768574_2.fastq.gz | Fastqsanger.gz | |||
| SRR10768575_1.fastq.gz | Fastqsanger.gz | |||
| SRR10768575_2.fastq.gz | Fastqsanger.gz | |||
| SRR10768576_1.fastq.gz | Fastqsanger.gz |
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Project description:Macrophages have plasticity to adapt microenvironment. In joint tissue, synovial macrophages (SM) and synovial fibroblasts (SF) are maintained in the homeostasis. In Rheumatoid arthritis, crosstalk between SM and SF via inflammatory response induce abnormal activation in respective cells and contribute to disease progression. However, the activation mechanisms in SM which are encouraged by SF are largely unclear. Here, we demonstrated metabolic reprogramming and immunological activation in SM by secretary stimulations from SF using primary culture synovial cell derived from arthritis model mice. To analyze interaction between SM and SF, primary culture of murine synovial cells was performed, respectively. RNA-seq analysis showed SF express abundant secretion-related gene. Thus, we investigated whether conditioned medium from SF (SF-CM) affects biological activity in SM. As the results, SF-CM condition induced both glycolysis and mitochondrial respiration to SM with increased uptake of glucose and glutamine at least, accompanied with cell survival. In addition, several inflammation markers were also upregulated in SM by SF-CM condition. Taken together, these results suggest that metabolic reprogramming were induced in SM by secretory stimulations from SF, followed by activated inflammatory response and long-live. These indicate that such phenotypes of SM may contribute to chronic inflammation in Rheumatoid arthritis
2020-12-09 | GSE142607 | GEO
Project description:BackgroundMacrophages adapt to microenvironments, and change metabolic status and functions to regulate inflammation and/or maintain homeostasis. In joint cavities, synovial macrophages (SM) and synovial fibroblasts (SF) maintain homeostasis. However, under inflammatory conditions such as rheumatoid arthritis (RA), crosstalk between SM and SF remains largely unclear.MethodsImmunofluorescent staining was performed to identify localization of SM and SF in synovium of collagen antibody induced arthritis (CAIA) model mice and normal mice. Murine arthritis tissue-derived SM (ADSM), arthritis tissue-derived SF (ADSF) and normal tissue-derived SF (NDSF) were isolated and the purity of isolated cells was examined by RT-qPCR and flow cytometry analysis. RNA-seq was conducted to reveal gene expression profile in ADSM, NDSF and ADSF. Cellular metabolic status and expression levels of metabolic genes and inflammatory genes were analyzed in ADSM treated with ADSM-conditioned medium (ADSM-CM), NDSF-CM and ADSF-CM.ResultsSM and SF were dispersed in murine hyperplastic synovium. Isolations of ADSM, NDSF and ADSF to analyze the crosstalk were successful with high purity. From gene expression profiles by RNA-seq, we focused on secretory factors in ADSF-CM, which can affect metabolism and inflammatory activity of ADSM. ADSM exposed to ADSF-CM showed significantly upregulated glycolysis and mitochondrial respiration as well as glucose and glutamine uptake relative to ADSM exposed to ADSM-CM and NDSF-CM. Furthermore, mRNA expression levels of metabolic genes, such as Slc2a1, Slc1a5, CD36, Pfkfb1, Pfkfb3 and Irg1, were significantly upregulated in ADSM treated with ADSF-CM. Inflammation marker genes, including Nos2, Tnf, Il-1b and CD86, and the anti-inflammatory marker gene, Il-10, were also substantially upregulated by ADSF-CM. On the other hand, NDSF-CM did not affect metabolism and gene expression in ADSM.ConclusionsThese findings suggest that crosstalk between SM and SF under inflammatory conditions can induce metabolic reprogramming and extend SM viability that together can contribute to chronic inflammation in RA. Video Abstract.
| S-EPMC7708128 | biostudies-literature
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 role of synovial tissue fibroblasts and macrophages interactions in driving chronic inflammation and resolution of arthritis is unknown. In this project, we used bulk RNAseq to investigate the impact of different phenotypes of macrophages on activation of synovial fibroblasts.
2020-04-18 | E-MTAB-8316 | biostudies-arrayexpress
Project description:Gene expression profile of BMS-470539 on human synovial fibroblasts.
2019-12-16 | GSE98658 | GEO
Project description:mRNA expression levels in synovial fibroblasts in 6 rheumatoid arthritis patients versus 6 osteoarthritis patients. Keywords: disease type comparison, mRNA expression study
2007-08-30 | GSE7669 | GEO
Project description:The aim of this study was to compare the gene expression pattern of synovial cells from inflammatory (I) or normal/reactive (N/R) areas of a synovial membrane harvested from the same osteoarthritis (OA) patient. This study is the first to identify different expression pattern between two areas of the synovial membrane in the same patient. These differences concern several key pathways involved in OA pathogenesis (inflammation, cartilage metabolism, Wnt signaling and angiogenesis). This analysis also provides interesting information regarding new potent intermediates as potentiel targets for the future therapeutic. Synovial tissues were obtained from 12 knee OA patients at the time of total knee replacement. The inflammatory status of the synovial membrane was characterized according to macroscopic criteria and sorted as N/R and I. Biopsies were cultured separately for 7 days. Microarray gene expression profiling between N/R and I areas was performed.
2013-05-20 | E-GEOD-46750 | biostudies-arrayexpress
Project description:To investigate the effects of soluble factors produced by synovial CD8 T cells, we stimulated human rheumatoid arthritis (RA) synovial fibroblasts with supernatants from synovial fluid CD8 T cells, blood CD8 T cells, or synovial fluid CD4 T cells stimulated with anti-CD3/CD28 antibody-coated beads. For comparison, we stimulated RA synovial fibroblasts with recombinant TNF or interferon-gamma or T cell supernatants pre-incubated with TNF-blocking antibodies.
2022-05-08 | GSE202367 | GEO
Project description:The synovium secretes synovial fluid but is also richly innervated with nociceptors and acts as a gateway between avascular joint tissues and the circulatory system. Resident fibroblast-like synoviocytes’ (FLS) calcium-activated potassium channels (KCa) change in activity in arthritis models and this correlates with FLS activation. To deepen our understanding of the synovium in the context of synovial joint health and disease, the electrophysiological profile of FLS cells needs to be characterised, along with the ion channels that are present. Ion channels are an essential component of any cell membrane that controls ion movement in and out of the cell and play an important role in a multitude of cell regulating processes, typically by modulating the membrane potential To this end, we chose to perform an UNBIASED screen to identify/screen the ion channels that are transcribed in these cells and determine if this "channelome" changes with cytokine exposure. PCR/Westerns naturally bias toward the known proteins and transcripts and so we used Next Generation sequencing to scan the entire transcriptome. Objective: To determine the mechanism of this activation in an in vitro model of inflammatory arthritis; 72hr treatment with the cytokines TNFa and IL1b.
2020-03-06 | E-MTAB-7798 | biostudies-arrayexpress