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Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

ABSTRACT: Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

PROVIDER: PRJNA896201 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR22112712_1.fastq.gz	Fastqsanger.gz
	SRR22112712_2.fastq.gz	Fastqsanger.gz
	SRR22112713_1.fastq.gz	Fastqsanger.gz
	SRR22112713_2.fastq.gz	Fastqsanger.gz
	SRR22112714_1.fastq.gz	Fastqsanger.gz

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Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

Project description:To investigate differences in gene expression of synovial macrophages in experimental rat knee post traumatic osteoarthritis.

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Complexity of synovial fluid-derived monocyte–macrophage lineage cells in knee osteoarthritis

Project description:Complexity of synovial fluid-derived monocyte–macrophage lineage cells in knee osteoarthritis

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Identification of synovial fibroblasts subsets associated with pain and progression of knee osteoarthritis

Project description:Background: Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas associated with pain exhibited different synovial fibroblast transcriptomes, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblasts. Methods: Patients with early knee OA (n=29) and end-stage knee OA (n=22) were recruited. Patient reported pain was recorded by questionnaire and using an anatomical knee pain map. Proton density fat suppressed MRI axial and sagittal sequences were analysed and scored for synovitis. Synovial tissue was obtained from the medial and lateral parapatellar and suprapatellar sites. RNA sequencing was performed using Illumina’s NextSeq 500 and analysed with Galaxy web platform, usegalaxy.org, and Qlucore software. Transcriptomes were functionally characterised using Ingenuity Pathway Analysis. Findings: Parapatellar synovitis was significantly associated with increased OA pain perception. Functional pathway analysis revealed that early OA painful sites mediate immune cell recruitment and promote the formation and development of neurites. Conclusion: OA disease progression and the presence of pain in early OA is associated with different synovial pathotypes. Further interrogation of these pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting to alleviate pain in patients.

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Bulk RNA-seq of human knee osteoarthritis synovium

Project description:To classify knee osteoarthritis (OA) synoviums according to gene expression patterns, we performed RNA-seq using synovial tissues obtained from OA patients and non-OA patients.

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Project description:Synovial fluid (SF)-derived monocyte–macrophage lineage (MON–Mϕ) cells in knee osteoarthritis (KOA) remain poorly understood. This lineage consists of four subpopulations with considerable interindividual variability that correlates with the distribution and activation of other immune cells. The most abundant subpopulation was that of CD11b+CD14−CD16− myeloid dendritic cells (mDCs; type cDC2), which were inactive and exhibited low cytokine production, low T-lymphocyte stimulation, high migratory ability comparing to other MON–Mϕ cells. Other major subpopulations included CD11b+CD14+CD16− monocyte-like cells and CD11b+CD14+CD16+ macrophages. A subpopulation of CD11b−CD14−CD16− mDCs (type cDC1) was less common. To confirm the identity of MON–Mϕ subpopulations characterised through flow cytometry, we performed bulk RNA-seq analysis on sorted CD11b+CD14−CD16−, CD11b+CD14+CD16− and CD11b+CD14+CD16+ MON–Mϕ subpopulations from the SF of four patients with KOA with a predominance of MON–Mϕ lineage cells. The CD11b+CD14+CD16− and CD11b+CD14+CD16+ cells shared a similar transcriptomic profile. However, CD11b+CD14−CD16− cells were remarkably distinct from other CD11b+ populations. The dataset is part of a study published by Mikulkova et al. Cell Reports.

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Project description:To classify knee osteoarthritis (OA) synoviums according to gene expression patterns, we performed single cell RNA-seq using synovial tissues obtained from OA patients.

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Transcriptome sequencing of synovial tissues of knee osteoarthritis rats.

Project description:Transcriptome sequencing of synovial tissues of knee osteoarthritis rats.

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Gene expression in synovial membranes from patients with early and end-stage osteoarthritis

Project description:Osteoarthritis is characterized by degeneration of cartilage and bone in the synovial joints. Recent findings suggest that inflammation may play a role in osteoarthritis, with synovitis being associated with the clinical symptoms of osteoarthritis. Furthermore, we have found that levels of inflammatory complement components are abnormally high in the synovial fluid of individuals with osteoarthritis. To determine whether synovial membranes could be a source of complement and other inflammatory molecules in osteoarthritic joints, we characterized the expression of genes in synovial membranes from patients with early-stage or end-stage osteoarthritis. Samples of synovial membrane were obtained from the suprapatellar pouch of patients with osteoarthritis who were treated at the Hospital for Special Surgery. Specifically, samples were from 10 patients with early-stage knee osteoarthritis who were undergoing arthroscopic procedures for degenerative meniscal tears (with documented cartilage degeneration but no full-thickness cartilage loss, Kellgren Lawrence score </=2), and from 9 patients with end-stage knee osteoarthritis ( diffuse full thickness cartilage erosion) who were undergoing total knee joint replacement. Raw data from microarray analysis of healthy synovial membranes, which were run on the same platform and array as our osteoarthritic samples, were downloaded from the NCBI Gene Expression Omnibus (accession number GSE12021) and used for comparison. The 19 new Samples of this Series were analyzed (RMA) together with 7 previously submitted healthy individual Samples (GSM175810, GSM175812, GSM176290, GSM176291, GSM176292, GSM176268, GSM176269). The complete RMA data are provided as a supplementary file on the Series record. The GSE12021 reanalyzed data are also provided as a supplementary file on the Series record. GSE32317_12genes.txt includes data from figure 1 of the paper.

2011-11-01 | E-GEOD-32317 | biostudies-arrayexpress

Identification of distinct synovial fibroblast subsets associated with pain and progression of knee osteoarthritis using single-cell RNA sequencing

Project description:Synovial inflammation is associated with pain severity in patients with knee osteoarthritis (OA). The aim here was to determine in a population with knee OA, whether synovial tissue from areas associated with pain exhibited different synovial fibroblast subsets, compared to synovial tissue from sites not associated with pain. A further aim was to compare differences between early and end-stage disease synovial fibroblast subsets. Parapatellar synovitis was significantly associated with the pattern of patient-reported pain in knee OA patients. Synovial tissue from sites of patient-reported pain exhibited a differential transcriptomic phenotype, with distinct synovial fibroblast subsets in early OA and end-stage OA. Functional pathway analysis revealed that synovial tissue and fibroblast subsets from painful sites promoted fibrosis, inflammation and the growth and activity of neurons. The secretome of fibroblasts from early OA painful sites induced neurite outgrowth in dorsal root ganglion neurons. Sites of patient-reported pain in knee OA is associated with a different synovial tissue phenotype and distinct synovial fibroblast subsets. Further interrogation of these fibroblast pathotypes will increase our understanding of the role of synovitis in OA joint pain and provide a rationale for the therapeutic targeting of fibroblast subsets to alleviate pain in patients.

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Transcriptome sequencing of synovial tissues of knee osteoarthritis rats.

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