Synovial Dysregulation in Ankle Osteoarthritis: Molecular Insights and Pathogenetic Pathways [RNA-Seq 1]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE293276 | GEO | 2025/07/03
REPOSITORIES: GEO
Similar Datasets
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
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.
2016-06-02 | GSE82107 | GEO
Project description:Synovial Dysregulation in Ankle Osteoarthritis: Molecular Insights and Pathogenetic Pathways [RNA-Seq 1]
| PRJNA1243472 | ENA
Project description:Increased interleukin (IL)-17A has been identified in joints affected by osteoarthritis (OA), but it is unclear how IL-17A, and its family members IL-17AF and IL-17F, can contribute to human OA pathophysiology. Therefore, we aimed to evaluate the gene expression and signalling pathway activation effects of the different IL-17 family members in chondrocytes and fibroblasts derived from cartilage and synovium of patients with end-stage knee OA. Chondrocytes and synovial fibroblasts derived from end-stage OA patients were treated with IL-17A, IL-17AF, or IL-17F, and gene expression was assessed with bulk RNA-Seq. Hallmark pathway analysis showed that IL-17 cytokines regulated several OA pathophysiology-related pathways including immune-, angiogenesis-, and complement-pathways in both chondrocytes and synovial fibroblasts derived from end-stage OA patients. While overall IL-17A induced the strongest transcriptional response, followed by IL-17AF and IL-17F, not all genes followed this pattern. Disease-Gene Network analysis revealed that IL-17A-related changes in gene expression in these cells are associated with experimental arthritis, knee arthritis, and musculoskeletal disease gene-sets. In conclusion, the association of IL-17-induced transcriptional changes with arthritic gene-sets supports a role for IL-17A in OA pathophysiology.
2021-06-02 | GSE171952 | GEO
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
Project description:Borreliella burgdorferi is the causative agent of Lyme disease, which is the most common vector-borne disease in the United States. While cases of Lyme disease are geographically limited to the Northeast, mid-Atlantic, and Midwest states, there are still estimates of almost 500,000 cases annually in the United States alone. In this study, we sought to assess transcriptional changes that occur in response to B. burgdorferi infection in the ankle joints of C57BL/6 mice. To this end, we performed single cell RNA sequencing (scRNA-seq) to transcriptionally profile cells, identify population heterogeneity, and analyze how cellular environments change over time. Sequencing of immune and non-immune cells in the mouse ankle joint was performed over five distinct time points, starting with uninfected animals and progressing to eight weeks post-infection in two-week increments.
2023-11-01 | GSE233850 | 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:Evidences indicate that mechanical loading plays an important role in osteoarthritis (OA) progression, while the specific pathological changes of the synovium under excessive mechanical loading are unclear. Results showed excessive mechanical loading caused pro-inflammatory of synovial macrophages, which has been confirmed to exists in OA. High Rapgef3 expression level was found in RNA sequencing of RAW246.7 subjected to 0.5Hz-20%-cyclic tensile strain. We verified this in the synovium of OA patients and DMM-OA mice. Interestingly, the Rapgef3 content of chondrocytes was very low. Primary chondrocytes treated with Rapgef3 alone did not show metabolic phenotype, but an OA phenotype appeared when treated with Rapgef3-stimulated macrophage culture supernatant. Mechanically, excessive mechanical loading activated p65-NF-κB pathway through Rapgef3, which promoted the inflammatory of macrophage, resulting in severe articular cartilage injury. Intra-articular Rapgef3 knockout reversed synovitis and cartilage degeneration, which might provide a therapeutic target for osteoarthritis.
2024-11-04 | GSE280230 | GEO
Project description:The Infrapatellar fat pads (IFP) are two wedge shaped fatty structures situated below the kneecap (patella), lying either side of the patellar tendon, first described by Hoffa in 1904. Recent studies reveal that knee OA causes pathological fibrosis, stiffening, and inflammation of the synovium and IFP (4, 5) (6). Multiple groups, including our co-investigator Dr. Changhai Ding, reported that MRI signal intensity alteration in IFP is strongly associated with OA knee structural abnormalities and may serve as an imaging biomarker to predict OA progression in patients (7-10). However, we have limited knowledge regarding the regulation of synovium and IFP functions for joint homeostasis and OA development.
2024-03-07 | GSE231755 | GEO
Project description:Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, has gained attention as a promising therapeutic target in osteoarthritis (OA) due to its central role in modulating inflammation, catabolism, and hypertrophy within chondrocytes. Previous studies have further demonstrated that EZH2 inhibition can slow OA progression in surgically induced mouse models, highlighting its potential in reducing joint degradation. However, the precise mechanisms by which EZH2 influences other key cell types in OA pathology remain poorly understood. In this study, we aimed to evaluate the effects of EZH2 inhibition in an alternative OA model and investigate its broader impact on cellular and molecular pathways across various tissues involved in OA progression and joint pain. OA was induced in mice via intra-articular injection of monosodium iodoacetate (MIA), with disease progression evaluated by histological and behavioral assessments. In parallel, human synoviocytes and bone marrow-derived cells were isolated from OA patients. Synoviocytes were stimulated with interleukin-1β (IL-1β) in the presence or absence of the EZH2 inhibitor EPZ-6438 (Tazemetostat), and ChIP-Seq and proteomic analyses were conducted to identify genomic and proteomic targets of EZH2. Additionally, the effects of EZH2 inhibition on M1 macrophage polarization and osteoclast differentiation were analyzed. Results revealed that EZH2 inhibition attenuated both OA progression and joint pain in the MIA-induced mouse model. IL-1β stimulation significantly upregulated EZH2 expression in synoviocytes, and treatment with the EZH2 inhibitor reduced the expression of genes linked to inflammation, pain, and catabolism while promoting autophagy. Proteomic analysis highlighted significant alterations in pathways related to IL-1β signaling, matrix metalloproteinase (MMP) activation, and autophagy, as well as changes in proteins associated with metabolic regulation and axon guidance. Importantly, EZH2 inhibition decreased M1 macrophage polarization and osteoclast formation, cellular processes that contribute to OA pain and inflammation. In conclusion, this study underscores the pivotal role of the histone methyltransferase EZH2 in the pathophysiology of osteoarthritis and associated joint pain. Our findings reveal that EZH2 inhibition not only attenuates inflammation in synovial cells and macrophages but also modulates axon guidance and osteoclastogenesis, both critical in OA progression and pain. These insights position EZH2 inhibition as a promising, multi-targeted therapeutic approach for addressing the complex cellular interactions underlying osteoarthritis, offering new hope for effective treatment strategies in this debilitating condition.
2025-06-30 | GSE300508 | GEO