Integrative analysis of bulk and single-cell RNA sequencing data reveals increased arachidonic acid metabolism in osteoarthritic chondrocytes DOI Creative Commons
Kan Xing Wu, Zhaoqian Zhong, Lixia Chen

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: May 9, 2025

Background Abnormal lipid metabolism in chondrocytes, especially arachidonic acid (AA) metabolism, has attracted considerable attention promoting osteoarthritis (OA) progression. However, the metabolic regulation of chondrocytes OA remains to be investigated. Methods Bulk RNA sequencing (RNA-seq) data and single-cell (scRNA-seq) human knee cartilage were downloaded from public databases. Gene set variation analysis (GSVA) weighted correlation network (WGCNA) used explore functional gene expression characterization. A reference Kyoto Encyclopedia Genes Genomes (KEGG) database was validate changes. CellChat performed investigate communication among osteoarthritic chondrocytes. Human immortalized stimulated with macrophage migration inhibitory factor (MIF), then quantitative real-time PCR (qPCR) western blot (WB) detect transcription or translation levels genes. Enzyme linked immunosorbent assay (ELISA) measure AA content. Cartilage patients collected for immunohistochemistry (IHC) protein expression. Results Functional revealed significant activation pathway significantly enriched cluster proliferative (ProCs). indicated that incoming signals MIF increased ProCs, expressions extracellular signal-regulated kinase (ERK) phospholipase A2 group IVA (PLA2G4A) upregulated. Moreover, showed ERK ProCs. Cell experiments stimulation elevated phospho-ERK (p-ERK) PLA2G4A IHC p-ERK activated cartilage. also upregulated interleukin 1β (IL1B) matrix metalloproteinase 13 (MMP13) Conclusion Our study shows can activate ERK/PLA2G4A signaling increase production. ProCs located layer are likely main cells executing this mechanism. Therefore, targeting inhibiting could a novel strategy prevention treatment OA.

Language: Английский

Integrative analysis of bulk and single-cell RNA sequencing data reveals increased arachidonic acid metabolism in osteoarthritic chondrocytes DOI Creative Commons
Kan Xing Wu, Zhaoqian Zhong, Lixia Chen

et al.

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 12

Published: May 9, 2025

Background Abnormal lipid metabolism in chondrocytes, especially arachidonic acid (AA) metabolism, has attracted considerable attention promoting osteoarthritis (OA) progression. However, the metabolic regulation of chondrocytes OA remains to be investigated. Methods Bulk RNA sequencing (RNA-seq) data and single-cell (scRNA-seq) human knee cartilage were downloaded from public databases. Gene set variation analysis (GSVA) weighted correlation network (WGCNA) used explore functional gene expression characterization. A reference Kyoto Encyclopedia Genes Genomes (KEGG) database was validate changes. CellChat performed investigate communication among osteoarthritic chondrocytes. Human immortalized stimulated with macrophage migration inhibitory factor (MIF), then quantitative real-time PCR (qPCR) western blot (WB) detect transcription or translation levels genes. Enzyme linked immunosorbent assay (ELISA) measure AA content. Cartilage patients collected for immunohistochemistry (IHC) protein expression. Results Functional revealed significant activation pathway significantly enriched cluster proliferative (ProCs). indicated that incoming signals MIF increased ProCs, expressions extracellular signal-regulated kinase (ERK) phospholipase A2 group IVA (PLA2G4A) upregulated. Moreover, showed ERK ProCs. Cell experiments stimulation elevated phospho-ERK (p-ERK) PLA2G4A IHC p-ERK activated cartilage. also upregulated interleukin 1β (IL1B) matrix metalloproteinase 13 (MMP13) Conclusion Our study shows can activate ERK/PLA2G4A signaling increase production. ProCs located layer are likely main cells executing this mechanism. Therefore, targeting inhibiting could a novel strategy prevention treatment OA.

Language: Английский

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