High throughput RNA-seq analysis in human primary chondrocytes treated with cyproheptadine and IL-1β
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE291878 | GEO | 2025/07/11
REPOSITORIES: GEO
Similar Datasets
Project description:Osteoarthritis (OA) is a joint condition associated with articular cartilage loss, low-grade synovitis and alterations in subchondral bone and periarticular tissues. In OA, the interest for mesenchymal stem cell (MSC)-EV therapeutic applications has increased. We have assessed the immunomodulary properties of adipose-derived MSCs (AD-MSCs) microvesicles (MV) and exosomes (EX) in interleukin (IL)-1β stimulated OA chondrocytes and cartilage explants and characterized them by mass spectrometry in order to uncover novel mediators in (AD-MSC)-EV immunomodulation.
2022-02-23 | PXD009077 | Pride
Project description:Inflammation, which is mainly sustained by pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6, plays an important role in osteoarthritis progression. However, the therapeutic failures of recent clinical trials evaluating anti-IL-1, anti-TNF, and anti-IL-6 drugs highlight the lack of overall understanding of the effects of these cytokines on chondrocytes. Here, we generated a comprehensive transcriptomic and proteomic dataset of osteoarthritic chondrocytes treated with these cytokines to describe their pro-inflammatory signature and compare it to the transcriptome of non-osteoarthritic chondrocytes. We first identified specific dysregulation of metabolic-related genes in OA chondrocytes. A metabolic shift, toward increased glycolysis at the expense of mitochondrial respiration, was specifically identified and confirmed by Seahorse® assay of osteoarthritic chondrocytes treated with IL-1β or TNF-α. These data show a strong association between inflammation and metabolism, indicating that understanding metabolic dysregulations should be a focus of future investigations for the design of therapies for osteoarthritis.
2023-05-20 | GSE215039 | GEO
Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA. Three samples of cultured chondrocytes from knee and proximal interphalangeal finger joints were compared. Gene expression of the four most differentially regulated genes was confirmed by real-time PCR in 10 independent samples.
2016-07-03 | E-GEOD-68038 | biostudies-arrayexpress
Project description:Osteoarthritis (OA) is a degenerative joint disease with a substantial health economic burden. There is no current treatment; instead, disease management targets the main symptoms (pain and stiffness) and culminates in joint replacement surgery. OA is a disease of cartilage degeneration, but the molecular changes leading to the development of OA are still poorly understood. In this study we compare methylation, gene transcription and protein abundance at the genome-wide level in individually-matched samples of chondrocytes extracted from affected and relatively healthy articular cartilage across 12 OA patients undergoing total knee replacement. Integration analysis highlights genes that are consistently affected at multiple levels, including AQP1, CLEC3B and COL1A1, and also relevant biological pathways such as extracellular matrix organization, collagen catabolism and proteolysis. Collectively these results provide a first view of the comprehensive molecular landscape underpinning OA development and point to potential therapeutic avenues.
2018-10-24 | PXD002014 | Pride
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:Osteoarthritis (OA) is a degenerative joint disease with limited effective therapies. Cold weathers have been shown to affect joint pain in OA patients. However, the impact of cold climate on OA progression is debated, with the underlying mechanisms not fully understood. To investigate the mechanisms by which low temperatures exacerbate OA, RNA sequencing on human chondrocytes cultured at 33 °C and 37 °C was performed. The gene expression in non-OA region chondrocytes and OA region chondrocytes at 33 °C was compared to that at 37 °C. The Apoe gene was identified as a temperature-relevant gene associated with exacerbation of osteoarthritis. Apoe expression was downregulated in both OA and non-OA chondrocytes cultured at 33°C compared to their 37°C counterparts.
2025-08-20 | GSE296344 | GEO
Project description:Osteoarthritis (OA) of the hand is a common disease resulting in pain and impaired function. The pathogenesis of hand OA (HOA) is elusive and models to study it have not been described so far. Culture of chondrocytes is a model to study the development of cartilage degeneration, which is a hallmark of OA and well established in OA of the knee and hip. In the current study we investigated the feasibility human chondrocyte culture derived from proximal interphalangeal (PIP) finger joints of dissecting room cadavers. Index and middle fingers without signs of osteoarthritis were obtained from 30 cadavers using two different protocols. Hyaline cartilage from both articulating surfaces of the proximal interphalangeal (PIP) joint was harvested and digested in collagenase. Cultured chondrocytes were monitored for contamination, viability, and expression of chondrocyte specific genes. Chondrocytes derived from knee joints of the cadavers were cultured under identical conditions. Gene expression comparing chondrocytes from PIP and knee joints was carried out using Affymetrix GeneChip Human 2.0 ST arrays. The resulting differentially expressed genes were validated by real-time PCR and immunohistochemistry.Chondrocytes harvested up to 101 hours after death of the donors were viable. mRNA expression of collagen 2A1, aggrecan and Sox9 was significantly higher in chondrocytes as compared to cultured fibroblasts. Comparison of gene expression by chondrocytes from PIP and knee joints yielded 528 differentially expressed genes. Chondrocytes from the same joint region had a higher grade of similarity than chondrocytes of the same individual. These results were validated using real-time PCR and immunohistochemistry.We demonstrate for the first time a reliable method for culture of chondrocytes derived from PIP joints. PIP chondrocytes show a specific gene expression pattern and could be used as tool to study cartilage degeneration in HOA.
2016-01-01 | GSE68038 | GEO
Project description:The phenotypic change of chondrocytes and the interplay between cartilage and subchondral bone in osteoarthritis (OA) has received much attention. Structural changes with nerve ingrowth and vascular penetration within OA cartilage may contribute to arthritic joint pain. The aim of this study was to identify differentially expressed genes and potential miRNA regulations in OA knee chondrocytes through next-generation sequencing and bioinformatics analysis. Results suggested the involvement of SMAD family member 3 (SMAD3) and Wnt family member 5A (WNT5A) in the growth of blood vessels and cell aggregation, representing features of cartilage damage in OA. Additionally, 26 dysregulated genes with potential miRNA⁻mRNA interactions were identified in OA knee chondrocytes. Myristoylated alanine rich protein kinase C substrate (MARCKS), epiregulin (EREG), leucine rich repeat containing 15 (LRRC15), and phosphodiesterase 3A (PDE3A) expression patterns were similar among related OA cartilage, subchondral bone and synovial tissue arrays in Gene Expression Omnibus database. The Ingenuity Pathway Analysis identified MARCKS to be associated with the outgrowth of neurite, and novel miRNA regulations were proposed to play critical roles in the pathogenesis of the altered OA knee joint microenvironment. The current findings suggest new perspectives in studying novel genes potentially contributing to arthritic joint pain in knee OA, which may assist in finding new targets for OA treatment.
2018-12-18 | GSE110606 | 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
Project description:Osteoarthritis (OA) is the most common joint disease, but there are currently no disease-modifying OA drugs (DMOADs) yet approved by the regulatory agencies. Regulating macrophage polarization can alleviate synovial inflammation and then repair articular cartilage damage, providing a new target for OA treatment. Here, we found that Skatole can modulate macrophage polarization and attenuate OA. Skatole hindered M1 macrophage polarization while promoting M2 macrophage polarization. Mechanistically, Skatole activated Stat6, suppressed the phosphorylation of IKK, IκBα, and p65 in NFκB signaling pathway, and inhibited MAPK signaling activation. RNA-seq analysis revealed that Skatole downregulated the expression of inflammation-related genes, while upregulating genes involved in glutathione metabolism and oxidative phosphorylation, thereby reducing ROS levels and inhibiting M1 macrophage polarization. Moreover, conditional medium (CM) from M1 macrophages treated with Skatole balanced anabolism and catabolism in mouse chondrocytes while inhibiting cell apoptosis. Intriguingly, in IL1β-treated chondrocytes, Skatole directly suppressed inflammation and catabolism, without significantly affecting cell apoptosis or anabolism; In vivo experiments showed that Skatole increased M2 polarization and decreased M1 polarization of synovial macrophages, alleviated synovitis, and lessend articular cartilage damage in destabilization of medial meniscus (DMM)-induced OA mice. Our finding suggest that Skatole has the potential to function as a DMOAD.
2025-02-12 | GSE261400 | GEO