Flightless I is a novel catabolic factor of chondrocytes that promotes hypertrophy and cartilage degeneration in osteoarthritis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA719424 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR14138147_1.fastq.gz | Fastqsanger.gz | |||
| SRR14138147_2.fastq.gz | Fastqsanger.gz | |||
| SRR14138148_1.fastq.gz | Fastqsanger.gz | |||
| SRR14138148_2.fastq.gz | Fastqsanger.gz | |||
| SRR14138149_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
Similar Datasets
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: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.
| S-EPMC8187833 | biostudies-literature
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:To underly the potential downstream transcriptional regulation of HPIP that could account for cartilage and skeletal development. RNA-seq analysis were performed in HPIP knockout and control primary chondrocytes.Among the 1271 significantly differentially expressed genes, transcripts for 486 (7%) of them were upregulated while transcripts for 785 (11%) were downregulated in HPIP knockout chondrocytes compared to the controls. We found HPIP was closely correlated with the cartilage development.
2017-06-23 | GSE100268 | GEO
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
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: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:Objectives: Understanding the molecular mechanisms underlying cartilage degeneration and regeneration is helpful for improving therapeutic strategies for treating osteoarthritis (OA). We report transcripts and pathways differentially expressed in chondrocytes obtained from genotypically and phenotypically distinct mouse strains. Methods: We performed RNA-sequencing and computational analysis on chondrocytes derived from LG/J (large, healer, n=16) and SM/J (small, non-healer, n=16) mouse strains. We validated the expression of candidate genes using real-time PCR and immunostaining. Results: Of those nearly 6,000 differentially expressed genes between LG/J and SM/J, 138 genes (99 protein-coding) were up-regulated and 145 (103 protein-coding) were down-regulated with log2 fold changes of 2 or more. Interestingly, we found the top up-regulated gene ontology biological pathways in the chondrocytes from the LG/J mice were related to chondrocyte development, cartilage condensation, and regulation of chondrocyte differentiation. In contrast, the top upregulated pathways in the SM/J mice were mostly inflammation related. Real-time PCR confirmed the expression pattern of a number of differentially expressed genes. Immunostaining of two candidate genes revealed that Tnfrsf23 and Car2 were respectively increased in LG/J and SM/J strains. Conclusions: The enrichment of genes and pathways related chondrocyte differentiation, cartilage development and cartilage condensation in LG/J appear to be responsible for their superior healing potential. The enrichment of pathways related to cytokine production, immune cell activation and inflammation in SM/J suggests a compromised chondrocyte proliferation and/or survival ability and a higher sensitivity to inflammation and OA. Tnfrsf23 and Car2 warrant further investigation to discern their specific role(s) in chondrocyte function and OA.
2020-03-17 | GSE128490 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2017-06-23 | GSE100312 | GEO
Project description:INTRODUCTION: Adiponectin has been implicated in the pathogenesis of osteoarthritis (OA). We studied the effects of adiponectin on the OA cartilage homeostasis. METHODS: Immunohistochemical analysis was performed to evaluate differential expression of adiponectin receptors (AdipoRs) in nonlesional and lesional areas of OA cartilage. Cartilage and chondrocytes from the knee joints of primary OA patients were cultured in the presence of adiponectin (0~30 ?g/ml). The levels of total nitric oxide (NO), matrix metalloproteinase (MMP)-1, -3, and -13, and tissue inhibitor of metalloproteinase (TIMP)-1 were measured in the conditioned media. The levels of inducible NO synthase (iNOS) and MMPs were determined with the quantitative real-time reverse transcription-polymerase chain reaction. The concentrations of collagenase-cleaved type II collagen neoepitope (C1-2C) were determined in the supernatant of adiponectin-stimulated OA cartilage explants. The effects of kinase and NOS inhibitors were evaluated in the adiponectin-stimulated chondrocytes. RESULTS: The expression levels of both AdipoR1 and AdipoR2 were significantly higher in lesional than in nonlesional areas of OA cartilage. The increased rate of AdipoR1-positive chondrocytes was twice that of AdipoR2-positive chondrocytes when compared between nonlesional and lesional areas. Adiponectin-stimulated OA chondrocytes showed increased total NO and MMP-1, -3, and -13 levels compared with nonstimulated cells. The TIMP-1 level was not affected. The C1-2C levels were increased by adiponectin in OA cartilage explant culture. AMP-activated protein kinase (AMPK) and c-Jun N-terminal kinase (JNK) inhibitors (compound C and SP600125) significantly suppressed adiponectin-induced production of total NO and MMP-1, -3, and -13. Inducible NOS inhibitors enhanced the expression of the adiponectin-induced MMPs. CONCLUSIONS: Adiponectin causes matrix degradation in OA cartilage and increases MMPs and iNOS expression via the AMPK and JNK pathways in human OA chondrocytes. The catabolic effects of adiponectin may be counteracted by NO.
| S-EPMC3046544 | biostudies-literature