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Extracellular vesicles derived from synovial inflammatory macrophages induce the onset of osteoarthritis in a FMRP-selectively sorted manner [RNA-seq]

ABSTRACT: Purpose:Next Generation Sequencing has revolutionized the effect of EVs secreted by synovial inflammatory macrophages on the cartilage of OA progression. The goals of this study are to compare NGS-derived cartilages transcriptome profiling (RNA-seq) between exosomes derived from synovial inflammatory macrophages and PBS treated OA rats model. The key biological processes and siginaling pathway were identified with immunofluorescence (IF), Transmission electron microscopy (TEM) and to evaluate protocols for optimal high-throughput data analysis.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE278832 | GEO | 2024/10/04

REPOSITORIES: GEO

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Extracellular vesicles derived from synovial inflammatory macrophages induce the onset of osteoarthritis in a FMRP-selectively sorted manner

Project description:Osteoarthritis (OA) is an aging-related degenerative joint disease without effective therapeutic. In the early stage of OA, mild synovitis has been proven to induce normal cartilage lesions. However, the mechanism is poorly defined. Here, we identified that the extracellular vesicles (EVs) derived from synovial inflammatory macrophages regulate the autophagy function of chondrocytes, acting as the dominant inducer of the onset of cartilage degeneration in normal and OA joints. Mechanistically, the active transfer of miR-155-5p via EVs from synovial inflammatory macrophages to chondrocytes accelerates cartilage degeneration by suppressing GSK 3β/mTORC1 axis-mediated autophagy function during OA progression.

2024-09-30 | GSE278392 | GEO

RNA-sequencing of highly pure synovial tissue macrophages reveals two distinct osteoarthritis subgroups that indicate different disease mechanisms.

Project description:Osteoarthritis (OA) is a leading cause of disability globally. Despite an emerging role for synovial inflammation in OA pathogenesis, attempts to target inflammation therapeutically have had limited success. A better understanding of the cellular and molecular processes occurring in the OA synovium is needed to develop novel therapeutic strategies. Here, we contrasted mononuclear phagocytes and T cells in the synovial tissue of OA patients and inflammatory-arthritis (IA) patients. Compared to IA, OA synovial tissue contained fewer CD45+ leukocytes, consisting mostly of macrophages. Macrophages in OA synovial tissues displayed activated phenotypes shown by expression of proteins folate-receptor-2 and CD86. Macrophage phenotype, proliferation characteristics and transcriptome profile by RNA-sequencing distinguished two subtypes of patients within OA. One subgroup was more similar to IA - ‘inflammatory-like OA’ (iOA), and another non-inflammatory/mechanical, subgroup distinct from IA - ‘classical OA’ (cOA). Gene Ontology (GO) pathway analysis revealed that the iOA subgroup is characterised by a cell proliferation signature, whereas the cOA subgroup is defined by cartilage remodelling features. Furthermore, iOA synovial tissue contained higher proportions of macrophages, expressing higher levels of the proliferation marker Ki-67, as compared to cOA synovial tissue. The identification of these two distinct OA subtypes provides new insight into the heterogeneity of OA at the synovial tissue level, and suggests distinct cellular mechanisms in disease pathogenesis. Our findings could lead to the stratification of OA patients for suitable disease-modifying treatments, and the identification of novel therapeutic targets.

2019-10-24 | GSE123492 | GEO

Synovial biopsies of osteoarthritis patients

Project description:Synovial biopsies were obtained from osteoarthritis (OA) synovium to find genes upregulated during OA. The genes upregulated during OA can be used to identify disease characteristic genes. 10 microarrays of end-stage OA synovial biopsies were compared to 7 microarrays of synovial biopsies from individuals without a joint disease. Genes with >1.2-fold upregulation and P<0.05 in OA VS HC were selected from the analysis.

2016-06-02 | E-GEOD-82107 | biostudies-arrayexpress

Gene expression pattern of synovial cells from inflammatory and normal areas of osteoarthritis synovial membrane

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

Synovial biopsies of osteoarthritis patients

2016-06-02 | GSE82107 | GEO

Gene expression pattern of synovial cells from inflammatory and normal areas of osteoarthritis synovial membrane

2013-05-20 | GSE46750 | GEO

Synovial fibroblasts from obese hip osteoarthritis patients exhibit distinct single-cell subsets characterised by pathological inflammatory functions

Project description:Inflammation of synovial tissue (synovitis) is a hallmark of osteoarthritis (OA) pathogenesis and is pronounced in obese individuals. The aim of this study was therefore to perform scRNA-seq analysis of synovial fibroblast from hip OA patients who were either obese or normal-weight to identify specific fibroblast subsets that exhibit disease-associated inflammatory functions. : scRNA-seq identified eight OA synovial fibroblast clusters, with distinct differences between obese and normal-weight patients. Fibroblast clusters in obese OA patients highly expressed gene signatures related to immune cell regulation, fibrosis and inflammatory signalling, including Chitinase3-like 1 (CHI3L1), CXCL12, osteonectin (SPARC), SMOC2 and Galectin-1 (LGALS1). Pseudotemporal expression dynamics demonstrated a transition in the expression of the transcriptional regulator MYC and Inhibin A in normal-weight clusters, and the expression of FOS and CHI3L1 in obese fibroblast clusters. Analysis of fibroblast conditioned media showed that obese OA fibroblasts secreted significantly greater amounts of CHI3L1, whilst normal-weight fibroblasts secreted greater amounts of Inhibin.

2020-10-31 | GSE152815 | GEO

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.

2021-10-20 | GSE176223 | GEO

Transcriptomic profiling of osteoarthritis synovial macrophages reveals a tolerized phenotype compounded by a weak corticosteroid response

Project description:It is well-known that long-term osteoarthritis prognosis is not improved by corticosteroid treatments. Here we investigate what could underlie this phenomenon by measuring the short term corticosteroid response of osteoarthritic joint synovial macrophages (OA-Mf).

2024-05-24 | GSE124928 | GEO

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.

2021-10-20 | GSE176308 | GEO

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