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Status |
Public on Sep 20, 2023 |
Title |
Inflammatory macrophage-derived extracellular vesicles trigger the non-canonical pyroptosis pathway in chondrocytes leading to cartilage catabolism and degeneration in osteoarthritis |
Organism |
Mus musculus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
RNA-seq for mouse chondrocytes stimulated with extracellular vesicles derived from inflammatory macrophage
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Web link |
https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42505
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Contributor(s) |
Ebata T, Alaa T, Matsumae G, Iwasaki N |
Citation(s) |
36924130 |
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Submission date |
Mar 22, 2022 |
Last update date |
Dec 20, 2023 |
Contact name |
Mohamad Alaa Terkawi |
E-mail(s) |
materkawi@med.hokudai.ac.jp
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Organization name |
Hokkaido University
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Department |
Department of Orthopedic Surgery
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Street address |
Kita-15, Nish-7, Kita-ku
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City |
Sapporo |
State/province |
Hokkaido |
ZIP/Postal code |
060-8638 |
Country |
Japan |
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Platforms (1) |
GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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Samples (6)
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GSM5966557 |
Mouse chondrocytes stimulated with M-EVs 1 |
GSM5966558 |
Mouse chondrocytes stimulated with M-EVs 2 |
GSM5966559 |
Mouse chondrocytes stimulated with M-EVs 3 |
GSM5966560 |
Mouse chondrocytes stimulated with M-LPS EVs 1 |
GSM5966561 |
Mouse chondrocytes stimulated with M-LPS EVs 2 |
GSM5966562 |
Mouse chondrocytes stimulated with M-LPS EVs 3 |
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Relations |
BioProject |
PRJNA818781 |