Bioinformatics and Experimental Validation of FLVCR1 and SOX4 in Regulating Mitochondria-Macrophage Crosstalk in Disc Degeneration

Ji Zhou,1 Yang Zheng,2 Xie Zheng,1 Chun-yan Chen,1 Su-cheng Ding,1 Rong Wang1 1People’s Hospital of Anji, Huzhou, People’s Republic of China; 2The Department of Orthopedics, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, People’s Republic of ChinaCorrespondence: Rong Wang, People’s Hospital of Anji, No. 699 Tianmu Road, Dipu Town, Anji County, Huzhou, People’s Republic of China, Tel +86-572-5022428, Email [email protected]: Intervertebral disc degeneration (IDD) is a prevalent cause of backache and disability in many people. Mitochondrial homeostasis and macrophage polarization may be pivotal in slowing IDD evolution, but the relationship between mitochondria related genes (MRGs) and macrophage polarization related genes (MPRGs) and IDD is still unclear. This research aims to elucidate the potential mechanism of MRGs and MPRGs during IDD progression through transcriptome data.Methods: Publicly available transcriptome datasets were analyzed to identify candidate genes through differential expression analysis, weighted gene co-expression network analysis, and machine learning. Key findings were further validated in an animal model of lumbar disc herniation. Immune infiltration analysis, regulatory network construction, drug prediction, and molecular docking were used to investigate underlying mechanisms and therapeutic potential.Results: Two genes, FLVCR1 and SOX4, were identified as central players. Immune analysis showed that FLVCR1 was strongly negatively correlated with monocytes (cor = − 0.76), while SOX4 was associated with multiple immune cell types. FOXC1 was identified as a shared transcription factor regulating both genes. Drug prediction suggested Remifentanil and MCDF as promising compounds, with molecular docking supporting the potential binding of Remifentanil to FLVCR1.Conclusion: This study highlights the potential roles of FLVCR1 and SOX4 in the development of IDD, providing a reference for the early diagnosis and precise treatment of patients with IDD.Keywords: intervertebral disc degeneration, mitochondria, macrophage polarization, key genes, transcriptomics