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

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

PROVIDER: PRJNA735405 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14740700.fastq.gz	Fastqsanger.gz
	SRR14740701.fastq.gz	Fastqsanger.gz
	SRR14740702.fastq.gz	Fastqsanger.gz
	SRR14740703.fastq.gz	Fastqsanger.gz
	SRR14740704.fastq.gz	Fastqsanger.gz

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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

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

Spatial profiling of synovial tissue from patients with late-stage knee osteoarthritis.

Project description:Marked changes in synovial tissue are seen in knee osteoarthritis and are related to pain; however, the regulation of these processes are not fully understood. Spatial profiling was used to characterize cellular profiles and biological processes within important microenvironments in the synovium (intimal lining, sub-lining, and vessels) between patients that experience more pain compared to those that experience less pain.

2025-04-21 | GSE248454 | GEO

Pain-driven transcriptome changes in synovium of knee osteoarthritis patients

Project description:Objectives : Joint pain causes a significant morbidity in osteoarthritis (OA). The synovium as an innervated joint structure might contribute to the peripheral pain in OA. Methods : We used a hypothesis-free next generation RNA sequencing to study protein coding and small non-coding transcriptomes in knee synovial tissues of OA patients (n=10) with high and low knee pain (evaluated by visual analogue scale) followed by Gene Ontology (GO) and pathway analyses and integration of mRNAs and small RNAs data sets. Results : We showed that 33 protein-coding genes and 35 small RNAs were differentially expressed in the knee synovium of patients with high compared to low intensity knee pain, with 30 mRNAs and 14 small RNAs being upregulated and 2 mRNAs and 21 small RNAs being downregulated. Top enriched genes, such as SDIM1 and CPE encode neuronal proteins that share molecular properties with neurotrophic factor BDNF and promote neuronal survival under cellular stress, and OTOF participates in calcium-dependent synaptic exocytosis and modulation of GABAergic activity. TrkB was enriched in several gene networks, suggesting its key role in pain-related transcriptional changes in OA joint. Downregulation of PTX3 in high pain group supports an argument that inflammation and pain are independent processes in symptomatic knee OA. MiR-146a-3p and miR150 appeared as the microRNA candidates in the pathogenesis of OA-related knee pain. Conclusions : Here we uncovered the molecular complexity of pain-related transcriptome changes in the synovium of knee joints in osteoarthritis. We identified new molecular candidates in OA pain setting a firm ground for future mechanistic studies and drug discovery in OA.

2018-11-05 | GSE99662 | GEO

Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

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

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

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Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis

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Gene expression profile at single cell level of synovial cells from patients with late-stage knee osteoarthritis

Project description:Innate immune cell are increased in the synovium in knee osteoarthritis. We used single cell RNA sequencing to analyze synovial cellular profiles, function, and biological processes.

2025-04-21 | GSE248453 | GEO

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.

2025-01-07 | GSE283079 | GEO

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