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Updated: May 10, 2026
Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
Integration of scRNA-seq and bulk RNA-seq reveals that macrophage ferroptosis inhibits MSC osteogenic differentiation
Jiabao Liu1, Shuanji Ou1, Jianping Wen1
1Department of Orthopaedics, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, 510317, Guangdong, China.
Background:
Bone infections disrupt bone homeostasis and impair regeneration. Ferroptosis is closely associated with bone homeostasis regulation. However, the molecular mechanisms of these effects remain unclear. The present study sought to investigate the impacts of macrophage ferroptosis on osteogenic regeneration under an inflammatory microenvironment.
Methods:
Single-cell and bulk RNA sequencing were used to assess cellular heterogeneity and ferroptosis gene expression during bone infection. In vivo, in vitro, and clinical sample analyses were performed to assess the impact of macrophage ferroptosis on PANoptosis and mesenchymal stem cell (MSC) osteogenic differentiation in the inflammatory microenvironment.
Results:
During bone infection, macrophages exhibit lipid peroxidation, reactive oxygen species accumulation, upregulated acyl-CoA synthetase long-chain family member 4 (Acsl4) and lysophosphatidylcholine acyltransferase 3 (Lpcat3), and downregulated glutathione peroxidase 4 (Gpx4) and macrophage migration inhibitory factor (Mif). Additionally, macrophage ferroptosis promoted M1 macrophage polarization, increased MSC PANoptosis, and inhibited bone regeneration in the inflammatory microenvironment.
Conclusion:
Inhibiting macrophage ferroptosis promoted the polarization of macrophages towards the M2 phenotype, alleviated MSC PANoptosis, and promoted bone regeneration in the inflammatory microenvironment. This study provides a novel perspective on the pathological mechanisms of bone infections and identifies potential therapeutic targets.
Insights
Inhibiting ferroptosis in macrophages aids bone infection recovery. This process reduces harmful inflammation and promotes bone regeneration by shifting macrophage behavior and protecting stem cells.
Area of Science:
- Biomedical Science
- Regenerative Medicine
- Immunology
Background:
- Bone infections disrupt bone homeostasis and regeneration.
- Ferroptosis, a regulated cell death, impacts bone homeostasis, but its role in bone infection is unclear.
- Investigating macrophage ferroptosis in inflammation is crucial for understanding bone regeneration.
Purpose of the Study:
- To investigate the impact of macrophage ferroptosis on osteogenic regeneration within an inflammatory microenvironment.
- To elucidate the molecular mechanisms linking macrophage ferroptosis to bone healing.
Main Methods:
- Utilized single-cell and bulk RNA sequencing to analyze ferroptosis gene expression and cellular heterogeneity.
- Conducted in vivo, in vitro, and clinical sample analyses.
- Assessed the effects of macrophage ferroptosis on PANoptosis and mesenchymal stem cell (MSC) osteogenic differentiation.
Main Results:
- Macrophage ferroptosis during bone infection involves lipid peroxidation, ROS accumulation, and altered gene expression (e.g., Acsl4, Lpcat3, Gpx4, Mif).
- Macrophage ferroptosis promoted M1 polarization, increased MSC PANoptosis, and inhibited bone regeneration.
- Observed specific molecular markers associated with ferroptosis in macrophages.
Conclusions:
- Inhibiting macrophage ferroptosis promotes M2 macrophage polarization, reduces MSC PANoptosis, and enhances bone regeneration.
- This study identifies macrophage ferroptosis as a key factor in bone infection pathology.
- Provides potential therapeutic targets for treating bone infections and improving bone regeneration.
