Related Experiment Video
Updated: Aug 8, 2026
Mesenchymal Stem Cell Regulation of Macrophage Phagocytosis; Quantitation and Imaging
Published on: July 16, 2021
Bilirubin reductase regulates macrophage senescence and modulates implant-associated Staphylococcus aureus
Jinye Zhang1, Xinyuan Mao2, Haonan Zheng3
1The First School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, China; Division of Orthopaedics and Traumatology, Department of Orthopedics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Bone and Cartilage Regenerative Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
Purpose:
Osteomyelitis (OM) remains difficult to diagnose early due to its heterogeneous pathology and reliance on invasive biopsy. This study aimed to identify reliable diagnostic biomarkers and explore their roles in macrophage senescence during OM pathogenesis.
Methods:
We integrated single-cell RNA sequencing, bulk transcriptomics, and senescence-related gene sets to identify key genes. A diagnostic model was constructed using 3 machine-learning algorithms. Mendelian randomization analysis was applied to infer causality. Biliverdin Reductase A (BLVRA)'s role in macrophage senescence was validated through in vitro and in vivo Staphylococcus aureus infection models.
Results:
Seven diagnostic biomarkers were identified, with a combined model showing high accuracy (area under the curve? > 0.96). Mendelian randomization analysis confirmed a causal effect of BLVRA on OM risk. Single-cell data revealed predominant BLVRA expression in macrophages. Experimental validation showed that Staphylococcus aureus infection upregulates BLVRA and promotes macrophage senescence.
Conclusion:
BLVRA is a causal mediator of OM linked to macrophage senescence. This multi-omics approach offers a basis for early diagnosis and suggests potential immunotherapeutic targets for OM.
