Synovial Macrophage Activation Profiles in Experimental Knee Osteoarthritis
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE216932 | GEO | 2024/03/22
REPOSITORIES: GEO
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Project description:Patients with anterior cruciate ligament (ACL) tears have a significantly increased risk for developing knee osteoarthritis. These injuries often result in a knee effusion in response to the injury. Early changes in these effusions could be informative regarding initial steps in the development of post traumatic osteoarthritis. The purpose of this study was to test the hypothesis that the proteomics of knee synovial fluid changes over time following ACL injury.
2022-06-23 | MSV000089716 | MassIVE
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
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
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
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 physiologic responses of whole osteoarthritic synovium to cycle tensile strain. We obtained 3 matched synovial tissue samples from 6 patients undergoing total knee arthroplasty, subjected them to cyclic tensile strain, and then performed gene expression profiling analysis using RNA seq from each cyclic tensile strain protocol.
2022-09-30 | GSE205196 | GEO
Project description:Cartilage destruction in osteoarthritis (OA) results from disturbed chondrocyte metabolism. Here, we used microarrays to show that TGF alpha and CCL2 are simultaneously upregulated in a rat model of OA and cooperate to drive cartilage degradation. The goals of the experiments included here were to a) characterize gene expression in knee joint articular chondrocytes at various stages of development of OA (2 and 8 weeks after surgical induction of OA), and b) to establish trends in gene expression among groups of genes related to the TGF alpha-EGFR axis, over time, in OA. The model chosen to study these results has been previously validated (Appleton, CT et al, 2007, Arthritis Rheum) and used to describe similar gene expression results at a different time point (4 weeks) after induction of OA. The rat model of OA involves surgical destabilization of the knee joint, followed by forced low-intensity mobilization over several weeks; a sham surgery is used as the control (representing a healthy non-OA knee joint) wherein a surgical incision is made but not structural (i.e. ligamentous) modification is made to the joint. Altogether, our data indicate that TGF and CCL2 cooperate to drive cartilage degradation in osteoarthritis. A total of 12 samples were analyzed. 3 replicates were used per condition: OA surgery at 2 weeks, OA surgery at 8 weeks, Sham (control) surgery at 2 weeks and Sham surgery at 8 weeks. Expression of OA samples was assessed relaitve to Sham (control) expression levels.
2012-11-15 | E-GEOD-42295 | biostudies-arrayexpress
Project description:We elucidated the molecular cross-talk between knee articular cartilage and paired synovium in n=3 individuals with knee osteoarthritis using the powerful tool of single-cell RNA-sequencing. Multiple cell types were identified based on profiling of 10,640 synoviocytes and 26,192 chondrocytes (11,579 chondrocytes from the diseased medial vs 14,613 chondrocytes from the relatively non-diseased lateral tibial plateau): 12 distinct synovial cell types and 7 distinct articular chondrocyte phenotypes from matched tissues. Intact cartilage was enriched for homeostatic and hypertrophic chondrocytes, while damaged cartilage was enriched for prefibro- and fibro-, regulatory, reparative and prehypertrophic chondrocytes. A total of 61 cytokines and growth factors were predicted to regulate the 7 chondrocyte cell phenotypes. Based on production by >1% of cells, 55% of the cytokines were produced by synovial cells (39% exclusive to synoviocytes and not expressed by chondrocytes) and their presence in osteoarthritic synovial fluid confirmed. The synoviocytes producing IL-1beta (a classic pathogenic cytokine in osteoarthritis), mainly inflammatory macrophages and dendritic cells, were characterized by co-expression of surface proteins corresponding to HLA-DQA1, HLA-DQA2, OLR1 or TLR2. Strategies to deplete these pathogenic intra-articular cell subpopulations could be a therapeutic option for human osteoarthritis.
2020-07-06 | GSE152805 | GEO
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
Project description:Cartilage destruction in osteoarthritis (OA) results from disturbed chondrocyte metabolism. Here, we used microarrays to show that TGF alpha and CCL2 are simultaneously upregulated in a rat model of OA and cooperate to drive cartilage degradation. The goals of the experiments included here were to a) characterize gene expression in knee joint articular chondrocytes at various stages of development of OA (2 and 8 weeks after surgical induction of OA), and b) to establish trends in gene expression among groups of genes related to the TGF alpha-EGFR axis, over time, in OA. The model chosen to study these results has been previously validated (Appleton, CT et al, 2007, Arthritis Rheum) and used to describe similar gene expression results at a different time point (4 weeks) after induction of OA. The rat model of OA involves surgical destabilization of the knee joint, followed by forced low-intensity mobilization over several weeks; a sham surgery is used as the control (representing a healthy non-OA knee joint) wherein a surgical incision is made but not structural (i.e. ligamentous) modification is made to the joint. Altogether, our data indicate that TGF and CCL2 cooperate to drive cartilage degradation in osteoarthritis.
2012-11-15 | GSE42295 | GEO