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Identification of TIPARP, BCL6 and PLIN2 as Potential Ferroptosisrelated Biomarkers for Osteoarthritis
Hanyu Wang1, Zhikang Chen2, Shikai Chen1
1Spine Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China.
Introduction:
Studies have shown that ferroptosis may be related to the occurrence of OA. This study aimed to identify Ferroptosis-related Genes (FRGs) in OA synovium and the Infrapatellar Fat Pad (IPFP) and to analyze the potential molecular mechanisms.
Methods:
The single-cell RNA sequencing (scRNA-seq) and gene expression microarray datasets used in this study were downloaded from public databases and systematically preprocessed for subsequent analytical procedures. The gene expression microarray dataset originated from human synovial samples, and scRNA-seq data were obtained from the IPFP and synovial tissues. Thereafter, the machine learning algorithms were applied to determine key FRGs. Thereafter, immune infiltration analysis and molecular docking were performed to reveal the molecular mechanism of the key FRGs in OA.
Results:
The hub genes in the green module were enriched in pathways associated with immune cells and cytokines/chemokines. Machine learning identified three key FRGs, including TCDD-inducible Poly (ADP-ribose) Polymerase (TIPARP), BCL6 Transcription Repressor (BCL6), and Perilipin 2 (PLIN2). All three genes showed lower expression in OA cases and were negatively correlated with immune infiltration. Further single- cell analyses revealed their expression in monocytes/macrophages and smooth muscle cells. Molecular docking revealed a stable binding between Vorinostat and BCL6.
Discussion:
This study identified TIPARP, BCL6, and PLIN2 as key FRGs in OA using WGCNA and machine learning algorithms. These genes were correlated with immune infiltration. Specifically, BCL6 stably bound to vorinostat, showing the potential to serve as a target for OA treatment. This study relies on bioinformatics analysis of public data and lacks experimental validation, with conclusions needing confirmation via functional assays and larger, well-annotated clinical cohorts.
Conclusion:
In conclusion, our study identified TIPARP, BCL6, and PLIN2 as potential key FRGs in OA, providing novel insights for understanding the pathogenesis of OA.