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Updated: Jan 14, 2026
Tissue Collection and RNA Extraction from the Human Osteoarthritic Knee Joint
Published on: July 22, 2021
Integrative Bulk and Single-Cell Transcriptomic Profiling Reveals Oxidative Stress-Related Genes and Potential
Jinhui Peng1, Jinzhong Chen2, Duan Gao3
1Department of Minimally Invasive Spine, Yulin Orthopedic Hospital of Integrated Traditional Chinese and Western Medicine, Yulin, Guangxi, China.
Abstract:
Osteoarthritis (OA) is increasingly recognized as a degenerative joint disease that leads to a serious problem of public health, yet the underlying molecular mechanisms remain incompletely understood. In this study, we integrated bulk and single-cell RNA sequencing (scRNA-seq) datasets from the Gene Expression Omnibus (GEO) to systematically investigate oxidative stress-related genes and pathways in OA. Gene set enrichment analysis (GSEA) revealed significant activation of oxidative stress signaling in OA cartilage tissues, with 58 differentially expressed oxidative stress-related genes identified. Subsequent LASSO regression analysis highlighted seven diagnostic genes (STC2, LSP1, COL6A1, FOS, SELENON, TP53, and HSPA8), which demonstrated robust diagnostic performance in both training and validation cohorts. Single-cell analysis further revealed cell-type-specific differences in oxidative stress activity, with homeostatic chondrocytes (HomCs) exhibiting the highest pathway scores. Among the identified genes, FOS emerged as a hub regulator, showing elevated expression in HomCs from OA samples and strong associations with immune infiltration and proinflammatory pathways. Functional assays demonstrated that FOS knockdown significantly attenuated IL-1β-induced oxidative stress, apoptosis, and inflammatory cytokine (interleukin-6 [IL-6] and tumor necrosis factor-alpha [TNF-α]) release in chondrocytes. Furthermore, molecular docking and dynamics simulations identified ursolic acid (UA) as a stable small-molecule FOS binder, and in vitro experiments confirmed its inhibitory effects on oxidative stress and inflammation, comparable to FOS silencing or pharmacological inhibition. Collectively, our findings suggest that oxidative stress-related genes, particularly FOS, play a central role in OA pathogenesis by linking redox imbalance to immune dysregulation and chondrocyte injury, and highlight UA as a potential therapeutic candidate for OA management.
Insights
This study reveals oxidative stress and the FOS gene are key drivers of osteoarthritis (OA) pathogenesis. Ursolic acid shows potential for treating OA by targeting FOS-mediated inflammation and oxidative stress.
Area of Science:
- Biochemistry
- Molecular Biology
- Genetics
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease with poorly understood molecular underpinnings.
- Oxidative stress is implicated in OA pathogenesis, but its specific molecular players and pathways require detailed investigation.
Purpose of the Study:
- To systematically investigate oxidative stress-related genes and pathways in OA using integrated transcriptomic data.
- To identify key diagnostic genes and potential therapeutic targets for OA management.
Main Methods:
- Integrated analysis of bulk and single-cell RNA sequencing (scRNA-seq) datasets.
- Gene Set Enrichment Analysis (GSEA), LASSO regression, and cell-type-specific expression analysis.
- Functional assays, molecular docking, and in vitro experiments to validate gene function and therapeutic potential.
Main Results:
- Significant activation of oxidative stress signaling in OA cartilage, with 58 differentially expressed genes identified.
- Seven diagnostic genes, including FOS, were identified with high diagnostic performance.
- FOS was identified as a hub regulator in homeostatic chondrocytes, linking oxidative stress to inflammation and immune infiltration.
- FOS knockdown and ursolic acid (UA) treatment attenuated OA-related cellular damage and inflammation.
Conclusions:
- Oxidative stress, particularly mediated by the FOS gene, plays a crucial role in OA pathogenesis.
- FOS connects redox imbalance to immune dysregulation and chondrocyte injury in OA.
- Ursolic acid is a promising therapeutic candidate for OA, targeting FOS-driven pathways.
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