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Expression profiling of ankle joint of a mouse model of gouty arthritis uncovers potential mechanisms involved in pain and inflammation

ABSTRACT: Gout arthritis (GA) is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. Treatment and long-term management for gout patients remain challenging. However, the pathogenesis of GA still remained largely unknown. The purpose of this study is to perform an expression profiling to identify genes related with GA in an animal model. Using a monosodium urate (MSU) crystals-induced GA model, we performed RNA-sequencing for the ankle joint of gout mice in different time points. Our results revealed transcriptional changes in the joint. We provided by far the first study to profile gene expression changes and pathway analysis of ankle joint in different time for investigating GA mechanisms. This work may provide novel insights into understanding the mysterious mechanisms underlying GA.

ORGANISM(S): Mus musculus

PROVIDER: GSE242872 | GEO | 2023/09/30

REPOSITORIES: GEO

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Systematic analysis of inflammation and pain pathways in a mouse model of gout

Project description:Gout is a prevalent and painful inflammatory arthritis, and its global burden continues to rise. Intense pain induced by gout attacks is a major complication of gout. Treatment and long-term management for gout patients remain challenging. Despite the discovery of many key immune response and inflammatory genes and pathways in gout, the molecular mechanisms of gout inflammation are still not entirely elucidated. Particularly, systematic studies of gout inflammation and pain are lacking. Using a monosodium urate (MSU) crystals-induced gout model, we performed genome-wide transcriptome analysis for the ankle joint, dorsal root ganglion (DRG), and spinal cord of gout mice. Our results revealed transcriptional changes in both the joint and the nervous system. Furthermore, through integrated analysis with public datasets of mouse inflammatory pain and neuropathic pain models, human GWAS, osteoarthritis (OA), and rheumatoid arthritis (RA), we identified common and unique features associated with acute gout inflammation and severe pain.

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Multimodal smart systems reprMultimodal smart systems reprogram macrophages and remove urate to treat gouty arthritisogram macrophages and remove urate to treat gouty arthritis

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Identification of novel monosodium urate crystal-induced mRNAs

Project description:Objective. To identify novel monosodium urate (MSU) crystal-induced mRNAs by transcript profiling of isolated murine air pouch membranes. Methods. Nine hours after injecting crystals into air pouches, membranes were meticulously dissected away from the adjacent soft tissues. mRNA expression differences between inflamed and control membranes were determined by oligonucleotide microarray analysis. Induction of selected mRNAs was validated by real-time relative quantitative reverse transcriptase PCR (qPCR) in pouch membranes and murine peritoneal macrophages. Results. Eleven of the 12 most highly upregulated mRNAs related to innate immunity and inflammation. They included mRNAs encoding histidine decarboxylase (the enzyme that synthesizes histamine), interleukin (IL)-6, the cell surface receptors PUMA-g and TREM-1, and the polypeptides Irg1 and PROK-2. MSU crystals induced dramatic rises in these mRNAs in the pouch membrane within 3-8 hours after the surge in pro-inflammatory cytokine (IL-6, IL-1beta and TNFalpha) and immediate early gene (Egr-1) transcription, which occurred 1h after crystal injection. MSU crystals induced these mRNAs in cultured macrophages with similar kinetics but lower fold changes. In keeping with their downregulation by MSU crystals according to the microarrays, qPCR confirmed that TREM-2 and granzyme D mRNAs decreased 79% and 94%, respectively, in MSU crystal inflamed membranes. Conclusions. This analysis disclosed several genes previously not implicated in MSU crystal inflammation. Their rise after the early surge in cytokine mRNAs suggests that they may, for instance, amplify or perpetuate inflammation. Transcript profiling of the isolated air pouch membrane promises to be a powerful tool to identify genes acting at different stages of inflammation.

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