ArticleJournal of inflammation research2025
Comprehensive Analysis of Programmed Cell Death-Related Genes in Diagnosis and Synovitis During Osteoarthritis Development: Based on Bulk and Single-Cell RNA Sequencing Data.
Article in Journal of inflammation research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- ATP-P2X7R-NLRP3 Axis as a Unifying Mechanism of ATP-Induced Cell Death in Degenerative Bone and Cardiovascular Diseases.Journal of inflammation research · 2026Review
- A Novel Mitochondria-Associated Programmed Cell Death-Related Prognostic Model and Validation of Oncogene INHBB in Colorectal Cancer.International journal of genomics · 2025Article
- Retinoic Acid-Loaded Cartilage Organoids Attenuate Chondrocyte Senescence in Osteoarthritis.Journal of inflammation research · 2025Article
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Authors and funding
11 authors.
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Abstract
Background: Synovitis is one of the key pathological feature driving osteoarthritis (OA) development. Diverse programmed cell death (PCD) pathways are closely linked to the pathogenesis of OA, but few studies have explored the relationship between PCD-related genes and synovitis. Methods: The transcriptome expression profiles of OA synovial samples were obtained from the Gene Expression Omnibus (GEO) database. Using machine learning algorithms, Hub PCD-related differentially expressed genes (Hub PCD-DEGs) were identified. The expression of Hub PCD-DEGs was validated in human OA samples by qRT-PCR. A diagnostic model for OA was constructed based on the expression levels of Hub PCD-DEGs. Unsupervised consensus clustering analysis and weighted correlation network analysis (WGCNA) were employed to identify differential clustering patterns of PCD-related genes in OA patients. The molecular characteristics of Hub PCD-DEGs, their role in synovial immune inflammation, and their association with the immune microenvironment were investigated through functional enrichment analysis and ssGSEA immune infiltration analysis. Single-cell RNA sequencing analysis provided insights into the characteristics of distinct cell clusters in OA synovial tissues and their interactions with Hub PCD-DEGs. Results: We identified five Hub PCD-DEGs: TNFAIP3, JUN, PPP1R15A, INHBB, and DDIT4. qRT-PCR analysis confirmed that all five genes were significantly downregulated in OA synovial tissue. The diagnostic model constructed based on these Hub PCD-DEGs demonstrated diagnostic efficiency in distinguishing OA tissues as well as progression of OA. Additionally, a correlation was observed between the expression levels of Hub PCD-DEGs, immune cell infiltration, and inflammatory cytokine levels. We identified two distinct PCD clusters, each exhibiting unique molecular and immunological characteristics. Single-cell RNA sequencing further revealed dynamic and complex cellular changes in OA synovial tissue, with differential expression of Hub PCD-DEGs across various immune cell types. Conclusion: Our study suggests that PCD-related genes may be involved in development of OA synovitis. The five screened Hub PCD-DEGs (TNFAIP3, JUN, PPP1R15A, INHBB and DDIT4) could be explored as candidate biomarkers or therapeutic targets for OA.
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