Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA312193 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:To identify DOT1L targets, associated signaling pathways and networks in chondrocytes, we used genome-wide gene expression microarray analysis in human articular chondrocytes of 5 different donors (without known or documented joint disease) treated with EPZ-5676 or vehicle for 4 days. It is known that DOT1L inhibitors require longer time of treatment in order to show effect and influence the expression of MLL target genes in leukemia cells, but we opted for this relatively short inhibition time to be able to identify early changes induced by DOT1L inhibition. Human articular chondrocytes were obtained from 5 non-OA hip fracture patients. The cells were treated with 3 μM EPZ-5676 or vehicle (DMSO) for 4 days.
2017-04-20 | E-GEOD-77916 | biostudies-arrayexpress
Project description:To identify DOT1L targets, associated signaling pathways and networks in chondrocytes, we used genome-wide gene expression microarray analysis in human articular chondrocytes of 5 different donors (without known or documented joint disease) treated with EPZ-5676 or vehicle for 4 days. It is known that DOT1L inhibitors require longer time of treatment in order to show effect and influence the expression of MLL target genes in leukemia cells, but we opted for this relatively short inhibition time to be able to identify early changes induced by DOT1L inhibition.
2017-04-20 | GSE77916 | GEO
Project description:Osteoarthritis (OA) is the most common form of arthritis worldwide. It is a complex disease affecting the whole joint but is generally characterized by progressive degradation of articular cartilage. Recent genome-wide association screens have implicated distinct DNA methylation signatures in OA patients. We show that the de novo DNA methyltransferase (Dnmt) 3b, but not Dnmt3a, is present in healthy murine and human articular chondrocytes and expression decreases in OA mouse models and in chondrocytes from human OA patients. Targeted deletion of Dnmt3b in murine articular chondrocytes results in an early onset and progressive post-natal OA-like pathology. RNA-seq and MethylC-seq analyses of Dnmt3b loss-of-function chondrocytes shows that cellular metabolic processes are affected. Specifically, TCA metabolites and mitochondrial respiration are elevated. Importantly, a chondroprotective effect was found following Dnmt3b gain-of-function in murine articular chondrocytes in vitro and in vivo. This study shows that Dnmt3b plays a significant role in regulating post-natal articular cartilage homeostasis. Cellular pathways regulated by Dnmt3b in chondrocytes may provide novel targets for therapeutic approaches to treat OA.
2017-07-24 | GSE85148 | GEO
Project description:The aim of this study was to characterise the genome-wide DNA methylation profile of osteoathritis (OA) chondrocytes from both knee and hip cartilage, providing the first comparison of DNA methylation between OA and non-OA hip cartilage, and between OA hip and OA knee cartilage. The study was performed using the Illumina Infinium HumanMethylation450 BeadChip array. Genome-wide methylation was assesed in chondrocyte DNA extracted from 23 OA hip, 73 OA knee and 21 healthy hip controls (NOF - neck of femure samples). Keywords: Methylation profiling by array
2015-09-02 | GSE63695 | GEO
Project description:Developmental dysplasia of the hip (DDH) is one of the significant risk factors for hip osteoarthritis. In order to investigate the factors that induce early articular cartilage degeneration of the hip joints that are exposed to reduced dynamic loads arising from hip dislocation , we created rodent models of hip dislocation by swaddling. Notably, expression of periostin (Postn) was increased in the acetabular articular cartilage of the DDH models; Postn was a candidate gene associated with early articular cartilage degeneration. We showed that early articular cartilage degeneration was suppressed in Postn-/- DDH mice. Furthermore, a microgravity environment induced the expression of Postn in chondrocytes through STAT3 signaling. Postn induced catabolic factors, interleukin-6 and matrix metalloproteinase 3, in articular chondrocytes through integrin-nuclear factor κB signaling. Additionally, interleukin-6 stimulated Postn expression through STAT3 signaling. Thus, Postn plays a critical role in early articular cartilage degeneration associated with hip dislocation.
2022-07-20 | GSE173637 | GEO
Project description:As the unique cell type in articular cartilage, chondrocyte senescence is a crucial cellular event contributing to osteoarthritis development. Here we show that clathrin-mediated endocytosis and activation of Notch signaling promotes chondrocyte senescence and osteoarthritis development, which is negatively regulated by myosin light chain 3. Myosin light chain 3 (MYL3) protein levels decline sharply in senescent chondrocytes of cartilages from model mice and osteoarthritis (OA) patients. Conditional deletion of Myl3 in chondrocytes significantly promoted, whereas intra-articular injection of adeno-associated virus overexpressing MYL3 delayed, OA progression in male mice. MYL3 deficiency led to enhanced clathrin-mediated endocytosis by promoting the interaction between myosin VI and clathrin, further inducing the internalization of Notch and resulting in activation of Notch signaling in chondrocytes. Pharmacologic blockade of clathrin-mediated endocytosis-Notch signaling prevented MYL3 loss-induced chondrocyte senescence and alleviated OA progression in mice. Our results establish a previously unknown mechanism essential for cellular senescence and provide a potential therapeutic direction for OA.
2023-09-07 | PXD044684 | Pride
Project description:Autologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However, patients with osteoarthritis (OA) are lacking an appropriate long-lasting treatment alternative, partly since it is not known if chondrocytes from OA patients have the same chondrogenic differentiation potential as chondrocytes from donors not affected by OA. Articular chondrocytes from patients with OA undergoing total knee replacement (Mankin Score >3, Ahlbäck Score >2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and scaffold (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene expression profiling using genome-wide oligonucleotide microarrays. Expression data were verified by using quantitative RT-PCR. Chondrocytes from ND and OA donors demonstrated accumulation of comparable amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (COL2A1, COMP, aggrecan, CRTL1, SOX9) and genes involved in matrix synthesis (biglycan, COL9A2, COL11A1, TIMP4, CILP2) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (COL10A1, RUNX2, periostin, ALP, PTHR1, MMP13, COL1A1, COL3A1) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, were differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and only 184 genes were differentially regulated. Only few genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings suggest that the chondrogenic capacity is not significantly affected by OA and OA chondrocytes fulfill the requirements for matrix-associated ACT. Experiment Overall Design: Gene expression profiles of monolayer cultures (ML; passage 2) and Hyaff-11 scaffold cultures (3D; 14 days in vitro) of chondrocytes from 3 normal donors (ND; underwent ACT treatment) and 3 donors suffering from Osteoarthritis (OA; underwent knee replacement surgery) were determined. Comparative analyses between 3D and ML cultures (3D vs. ML) were performed to assess differentiation capacity of ND and OA chondrocytes. Furthermore, OA-related differences were determined comparing OA and ND monolayers as well as scaffold cultures (each OA vs. ND).
2009-09-13 | E-GEOD-16464 | biostudies-arrayexpress
Project description:We used chondrocytes exposed to osteoarthritic synovial fluid as a chronic disease model to study the effects of a chronic disease microenvironment on 2’-O-me rRNA heterogeneity. Human non-OA human articular chondrocytes (5 individual donors) were cultured either in the presence of OA-SF (20% (v/v), pool of 14 donors) or in a normal culture medium and were refreshed every other day. After 14 days of culture, RNA was isolated for 2’-O-methylation profiling of ribosomal RNAs.
2022-03-05 | E-MTAB-11469 | biostudies-arrayexpress
Project description:The aim of this study is to identify, for the first time, the genome-wide DNA methylation profiles of human articular chondrocytes from OA and healtly cartilage samples. A subsequent validation of methylation profiles were performed in an idependent cohort of OA samples with Affymetrix Hugene 1.1 st array This represents the gene expression component of the study only OA gene expression profiling was performed with Affymetrix Human Gene 1.1 st array was performed in and independent cohort of 23 OA patients
2013-04-01 | E-GEOD-43191 | biostudies-arrayexpress
Project description:Inflammatory mediators such as interleukin 6 (IL-6) are known to activate catabolic responses in chondrocytes during osteoarthritis (OA). This study aimed to investigate the downstream targets of IL-6 in murine chondrocytes. RNA-sequencing was performed in murine articular chondrocytes treated with IL-6 in hypoxia (1%O2) or normoxia (21%O2). RNA-sequencing revealed that SerpinA3N is a major target of IL-6 in articular chondrocytes. The expression of SerpinA3N was increased in OA cartilage and further investigated.
2024-07-31 | GSE271151 | GEO