SLC38A1 and STX11 are mitochondria-related biomarkers associated with immune infiltration in osteoarthritis

Wenxue Lv¹Mingxiu Yu^2,3Wenhai Yan¹Yuli Cai^1*Weiguo Wang^1,2*

• ¹Department of Orthopedics, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
• ²Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China
• ³Department of Ultrasound, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

Background: Mitochondrial dynamics and mitophagy play crucial roles in osteoarthritis (OA), yet specific contributions of mitochondrial dynamics-related genes (MD-RGs) and mitophagy-related genes (MP-RGs) remain unclear. This study aimed to elucidate precise mechanisms linking these genes in the context OA. Methods: OA-related transcriptome datasets and single-cell RNA sequencing (scRNAseq) dataset, incorporating MD-RGs and MP-RGs were utilized in this study. Hub genes were identified through differential expression analysis, weighted gene co-expression network analysis (WGCNA), and machine learning. Then the nomogram was constructed based on hub genes. Enrichment and immune infiltration analyses were performed on hub genes, and key cell types were identified based on hub gene expression. Finally, expression of hub genes was further verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Results: SLC38A1 and STX11 were identified as hub genes, linked to mitochondrial dynamics and mitophagy in OA. These genes enabled the construction of a reliable nomogram for predicting OA risk. Enrichment analysis revealed that the top biological processes converged on ECM-receptor interaction, underscoring its critical role in OA pathogenesis. Immune infiltration analysis uncovered significant disparities in ten immune cell types, including activated CD4 T cells and central memory CD4 T cells, between OA patients and healthy controls. The levels of these immune cells were strongly correlated with the expression of SLC38A1 and STX11. Additionally, endothelial cells, monocytes, and T cells emerged as key cellular players in OA. RT-qPCR validation showed that SLC38A1 was significantly downregulated in OA samples, while STX11 exhibited a similar trend, hinting at their potential roles in OA progress.This study identified SLC38A1 and STX11 as key genes linked to mitochondrial dynamics and mitophagy in OA. These findings provided a theoretical basis and reference value for diagnosis and treatment of OA.