Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Obesity defined molecular endotypes in the synovium of patients with osteoarthritis provides a rationale for therapeutic targeting of fibroblast subsets

ABSTRACT: This study aimed to establish molecular endotypes in osteoarthritis soft joint tissue driven by obesity in both load-bearing and non-load bearing joints. Transcriptomic analysis found the inflammatory landscape of OA synovial fibroblasts (SF) are independently impacted by obesity, joint loading, and anatomical site with significant heterogeneity between obese and normal weight patients. These findings demonstrate the significance of obesity in changing the inflammatory landscape of synovial fibroblasts in both load bearing and non-load bearing joints. The molecular endotypes identified may provide a route for the stratification of patients in clinical trials, providing a rational for the therapeutic targeting of specific SF subsets in specific patient populations with arthritic conditions.

ORGANISM(S): Homo sapiens

PROVIDER: GSE219027 | GEO | 2023/04/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Response of synovial fibroblasts to TNFα and IL6/sIL6R

Project description:Synovial fibroblasts (SF) are the main mesenchymal cell type constitutive in human synovial tissue. SF contribute to the homeostasis of normal joints by synthesizing extracellular matrix components and secreting the specific components of synovial fluid. SF are essential players in RA pathophysiology, they are the primary source of IL6 in the RA synovium contributing to perpetuate the inflammation in the joint. We used microarrays analysis to characterize the effector pro-inflammatory response of SF to TNFα and IL6/sIL6R signaling.

2021-06-01 | GSE132830 | GEO

The long-non coding RNA HOTAIR shapes the inflammatory response in joints of the lower extremity

Project description:Various forms of chronic arthritis like osteoarthritis (OA) or rheumatoid arthritis (RA) are major causes of disability and represent a global burden on health care systems. Inter- and intraindividual differences in the phenotype of arthritis often prevent early diagnosis and effective treatment. Previously, we suggested that site-specific differences in the joint stroma influence the development and the outcome of arthritis and showed that the long non-coding RNA HOTAIR is expressed exclusively in synovial fibroblasts (SF) of lower joints. Here, we further analysed the function of HOTAIR in SF and in arthritis development. We show that joint-specific HOTAIR expression in SF is stronlgy imprinted in the chromatin landscape of SF by epigenetic mechanisms. Nevertheless, HOTAIR expression in knee SF was downregulated by inflammatory cytokines. Accordingly, HOTAIR was more expressed in OA tissues than in RA tissues. Downregulation of HOTAIR regulated relevant arthritis pathways by epigenetic and transcriptional mechanisms and modified the migratory function of SF, decreased SF mediated osteoclastogenesis, and increased the attraction of B cells by SF. We propose that HOTAIR downregulation in inflammation epigenetically regulates important pathways and functions in SF, and thus modulates the phenotype of arthritis in lower extremity joints.

2023-01-01 | GSE185440 | GEO

Arthritis Flares Mediated by Tissue Resident Memory T Cells in the Joint

Project description:Rheumatoid arthritis is a systemic autoimmune disease, but disease flares typically affect only a subset of joints, distributed in a pattern that is distinctive for each patient. Pursuing this intriguing pattern, we show that arthritis recurrence is mediated by long-lived synovial resident memory T cells (TRM). In three murine models, CD8+ cells bearing TRM markers remain in previously inflamed joints during remission. These cells are bona fide TRM, exhibiting failure to migrate from joint to joint, preferential uptake of fatty acids, and long-term residency. Disease flares result from TRM activation by antigen, leading to CCL5-mediated recruitment of circulating effector cells. Correspondingly, TRM depletion ameliorates recurrence in a site-specific manner. Human rheumatoid arthritis joint tissues contain a comparable CD8+-predominant TRM population, most evident in late-stage leukocyte-poor synovium, exhibiting limited T cell receptor diversity and a pro-inflammatory transcriptomic signature. Together, these findings establish synovial TRM cells as a targetable mediator of disease chronicity in autoimmune arthritis.

2021-09-23 | GSE184582 | GEO

Transcriptome profiling to identify a human effector regulatory T cell core signature

Project description:We investigated the transcriptomic landscape of human Treg in an autoimmune-associated inflammatory environment, i.e. synovial fluid (SF) from inflamed joints of Juvenile Idiopathic Arthritis (JIA) to improve our understanding of human effector Treg programming.

2021-02-23 | GSE161426 | GEO

Equine synovial fluid

Project description:The aim of the study was to characterise the protein complement of synovial fluid (SF) in health and osteoarthritis (OA) using liquid chromatography mass spectrometry (LC-MS/MS) following peptide-based depletion of high abundance proteins. SF was used from nine normal and nine OA Thoroughbred horses. Samples were analysed with LC-MS/MS using a NanoAcquity™ LC coupled to a LTQ Orbitrap Velos. In order to enrich the lower-abundance protein fractions protein equalisation was first undertaken using ProteoMiner™. Progenesis-QI™ LC-MS software was used for label-free quantification. In addition immunohistochemistry, western blotting and mRNA expression analysis was undertaken on selected joint tissues.The number of protein identifications was increased by 33% in the Proteominer™ treated SF compared to undepleted SF. A total of 754 proteins were identified in SF. A subset of 10 proteins were identified which were differentially expressed in OA SF. S100-A10, a calcium binding protein was upregulated in OA and validated with western blotting and immunohistochemistry. Several new OA specific peptide fragments (neopeptides) were identified.The protein equalisation method compressed the dynamic range of the synovial proteins identifying the most comprehensive SF proteome to date. A number of proteins were identified for the first time in SF which may be involved in the pathogenesis of OA. We identified a distinct set of proteins and neopeptides that may act as potential biomarkers to distinguish between normal and OA joints.

2022-03-02 | PXD001509 | Pride

Epigenetic profiling to identify a human effector regulatory T cell core signature [H3K27ac]

Project description:We investigated the active enhancer landscape of human Treg in an autoimmune-associated inflammatory environment, i.e. synovial fluid (SF) from inflamed joints of Juvenile Idiopathic Arthritis (JIA) to improve our understanding of human effector Treg programming.

2021-02-23 | GSE156417 | GEO

Epigenetic profiling to identify a human effector regulatory T cell core signature [H3K4me1]

Project description:We investigated the gene expression profile and active enhancer landscape of human Treg in an autoimmune-associated inflammatory environment, i.e. synovial fluid (SF) from inflamed joints of Juvenile Idiopathic Arthritis (JIA) to improve our understanding of human effector Treg programming.

2021-02-23 | GSE156416 | GEO

Single Cell Analysis of adult zebrafish jaw joint

Project description:To profile the diversity of cell types present in adult zebrafish synovial joints, we performed single-cell RNA sequencing of the uninjured adult jaw joint and identified multiple skeletal, connective tissue, and fibroblast subtypes, including a joint-specific periosteal population.

2022-01-03 | GSE184403 | GEO

Metabolism in synovial macrophages are reprogrammed by synovial fibroblasts under inflammatory condition

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

Small non-coding RNAs in early equine osteoarthritis synovial fluid

Project description:Small RNA isolated from synovial fluid of the metacarpophalangeal joints of horses. Horses either had minimal signs of osteoarthritis based on macroscopic and microscopic joint scoring or early (mild) osteoarthritis. Differential expression of small non-coding RNAs was undertaken.

2020-06-30 | E-MTAB-8409 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data