Transcriptional profile of human macrophages stimulated by cartilage fragments
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE141308 | GEO | 2020/05/13
REPOSITORIES: GEO
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Project description:Transcriptional profile of human macrophages stimulated by cartilage fragments
| PRJNA593036 | ENA
Project description:Baker2017 - The role of cytokines, MMPs and
fibronectin fragments osteoarthritis
This model is described in the article:
Mathematical modelling of
cytokines, MMPs and fibronectin fragments in osteoarthritic
cartilage.
Baker M, Brook BS, Owen MR.
J Math Biol 2017 Feb; :
Abstract:
Osteoarthritis (OA) is a degenerative disease which causes
pain and stiffness in joints. OA progresses through excessive
degradation of joint cartilage, eventually leading to
significant joint degeneration and loss of function. Cytokines,
a group of cell signalling proteins, present in raised
concentrations in OA joints, can be classified into
pro-inflammatory and anti-inflammatory groups. They mediate
cartilage degradation through several mechanisms, primarily the
up-regulation of matrix metalloproteinases (MMPs), a group of
collagen-degrading enzymes. In this paper we show that the
interactions of cytokines within cartilage have a crucial role
to play in OA progression and treatment. We develop a
four-variable ordinary differential equation model for the
interactions between pro- and anti-inflammatory cytokines, MMPs
and fibronectin fragments (Fn-fs), a by-product of cartilage
degradation and up-regulator of cytokines. We show that the
model has four classes of dynamic behaviour: homoeostasis,
bistable inflammation, tristable inflammation and persistent
inflammation. We show that positive and negative feedbacks
controlling cytokine production rates can determine either a
pre-disposition to OA or initiation of OA. Further, we show
that manipulation of cytokine, MMP and Fn-fs levels can be used
to treat OA, but we suggest that multiple treatment targets may
be essential to halt or slow disease progression.
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2024-09-02 | BIOMD0000000928 | BioModels
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:To date, all of the prior osteoarthritic microarray studies in human tissue have focused on the overlying articular cartilage, meniscus, or synovium but not the underlying subchondral bone. In our previous study, our group developed a methodology for high quality RNA isolation from site-matched cartilage and bone from human knee joints, which allowed us to perform candidate gene expression analysis on the subchohndral bone (published on Osteoarthritis and Cartilage on Dec/5/2012 (doi: 10.1016/j.joca.2012.11.016). To the best of our knowledge, the current study is the first to successfully perform whole-genome microarray profiling analyses of human osteoarthritic subchondral bone. We believe our comprehensive microarray results can improve the understanding of the pathogenesis of osteoarthritis and could further contribute to the development of new biomarker and therapeutic strategies in osteoarthritis.
2013-10-24 | GSE51588 | GEO
Project description:The severity of osteoarthritis (OA) and cartilage degeneration are highly correlated with the development of synovitis, which is mediated by the activity of inflammatory macrophages. A better understanding of intercellular communication between inflammatory macrophages and chondrocytes should aid in the discovery of novel therapeutic targets. Here, we explored the pathological role of inflammatory macrophage-extracellular vesicles (EVs) in cartilage degeneration. Macrophages were stimulated by treatment with bacterial lipopolysaccharides to mimic the state of inflammatory macrophages and the resulting EVs (M-LPS EVs) were harvested for chondrocyte stimulation and intraarticular injection in a mouse model. This stimulation resulted in increased catabolism of chondrocytes and cartilage degeneration. Consistently, RNA-seq analyses of stimulated chondrocytes indicated that upregulated genes are mainly categorized into apoptotic process and TNF-signaling pathway which suggests the induction of apoptotic process. These chondrocytes exhibited a significant elevation in the expression of pyroptosis-related molecules that were correlated with the expression of chondrocyte catabolic factors. The disruption of caspase-11 significantly alleviated pyroptotic and catabolic processes in stimulated chondrocytes and the pathological changes in collagenase-induced OA model. Our results provide a new insight into the pathological mechanisms of OA and suggest that non-canonical pyroptosis signaling in chondrocytes represents an attractive therapeutic target for future treatment.
2023-09-20 | GSE199193 | GEO
Project description:Synovial macrophages that are activated by cartilage fragments initiate synovitis, a condition that promotes hypertrophic changes in chondrocytes leading to cartilage degeneration in OA. In this study, we analyzed the molecular response of chondrocytes under condition of this type of stimulation to identify a molecular therapeutic target. Stimulated macrophages promoted hypertrophic changes in chondrocytes resulting in production of matrix-degrading enzymes of cartilage. Among the top-upregulated genes, FliI was found to be released from activated chondrocytes and exerted autocrine/paracrine effects on chondrocytes leading to an increase in expression of catabolic and hypertrophic factors. Silencing FliI in stimulated cells significantly reduced expression of catabolic and hypertrophic factors in cocultured chondrocytes. Our further results demonstrated that the FliI-TLR4-ERK1/2 axis is involved in the hypertrophic signaling of chondrocytes and catabolism of cartilage. Our findings provide a new insight into the pathogenesis of OA and identify a potentially new molecular target for diagnostics and therapeutics.
2021-05-10 | GSE171420 | 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.
2011-11-01 | GSE32317 | GEO
Project description:To date, all of the prior osteoarthritic microarray studies in human tissue have focused on the overlying articular cartilage, meniscus, or synovium but not the underlying subchondral bone. In our previous study, our group developed a methodology for high quality RNA isolation from site-matched cartilage and bone from human knee joints, which allowed us to perform candidate gene expression analysis on the subchohndral bone (published on Osteoarthritis and Cartilage on Dec/5/2012 (doi: 10.1016/j.joca.2012.11.016). To the best of our knowledge, the current study is the first to successfully perform whole-genome microarray profiling analyses of human osteoarthritic subchondral bone. We believe our comprehensive microarray results can improve the understanding of the pathogenesis of osteoarthritis and could further contribute to the development of new biomarker and therapeutic strategies in osteoarthritis. Following histological assessment of the integrity of overlying cartilage and the severity of bone abnormality by microcomputed tomography, we isolated total RNA from regions of interest from human OA (n=20) and non-OA (n=5) knee lateral and medial tibial plateaus (LT and MT). A whole-genome profiling study was performed on an Agilent microarray platform and analyzed using Agilent GeneSpring GX11.5. Confirmatory quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis was performed on samples from nine OA individuals to confirm differential expression of 85 genes identified by microarray. Ingenuity Pathway Analysis (IPA) was used to investigate canonical pathways and immunohistochemical staining was performed to validate protein expression levels in samples.
2013-10-24 | E-GEOD-51588 | biostudies-arrayexpress
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:Osteoarthritis (OA) is an aging-related degenerative joint disease without effective therapeutic. In the early stage of OA, mild synovitis has been proven to induce normal cartilage lesions. However, the mechanism is poorly defined. Here, we identified that the extracellular vesicles (EVs) derived from synovial inflammatory macrophages regulate the autophagy function of chondrocytes, acting as the dominant inducer of the onset of cartilage degeneration in normal and OA joints. Mechanistically, the active transfer of miR-155-5p via EVs from synovial inflammatory macrophages to chondrocytes accelerates cartilage degeneration by suppressing GSK 3β/mTORC1 axis-mediated autophagy function during OA progression.
2024-09-30 | GSE278392 | GEO