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Series GSE199193 Query DataSets for GSE199193
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
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.
 
Overall design RNA-seq for mouse chondrocytes stimulated with extracellular vesicles derived from inflammatory macrophage
Web link https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.42505
 
Contributor(s) Ebata T, Alaa T, Matsumae G, Iwasaki N
Citation(s) 36924130
Submission date Mar 22, 2022
Last update date Dec 20, 2023
Contact name Mohamad Alaa Terkawi
E-mail(s) materkawi@med.hokudai.ac.jp
Organization name Hokkaido University
Department Department of Orthopedic Surgery
Street address Kita-15, Nish-7, Kita-ku
City Sapporo
State/province Hokkaido
ZIP/Postal code 060-8638
Country Japan
 
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM5966557 Mouse chondrocytes stimulated with M-EVs 1
GSM5966558 Mouse chondrocytes stimulated with M-EVs 2
GSM5966559 Mouse chondrocytes stimulated with M-EVs 3
Relations
BioProject PRJNA818781

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE199193_RAW.tar 12.7 Mb (http)(custom) TAR (of TXT)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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