The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis
<b>Background:</b> The immune response is essential for bone regeneration, and macrophages in the immune microenvironment contribute to bone metabolism and angiogenesis. Emerging evidence demonstrates that simvastatin is a promising candidate for bone repair and promotes bone formation b...
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2025-06-01
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| author | Siyu Zhu Yunmeng Tong Jiaqian Huang Yuzhu He Wenqi Fu Yaran Zang Huiying Liu |
| author_facet | Siyu Zhu Yunmeng Tong Jiaqian Huang Yuzhu He Wenqi Fu Yaran Zang Huiying Liu |
| author_sort | Siyu Zhu |
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| description | <b>Background:</b> The immune response is essential for bone regeneration, and macrophages in the immune microenvironment contribute to bone metabolism and angiogenesis. Emerging evidence demonstrates that simvastatin is a promising candidate for bone repair and promotes bone formation both in vitro and in vivo. However, the effect of simvastatin on macrophages and the following outcomes are still unclear. <b>Objectives:</b> This study aimed to investigate the potential immunomodulatory effect of simvastatin on M1 macrophages and its subsequent impact on osteogenesis and angiogenesis. <b>Methods:</b> Cell viability was assessed by CCK-8. Osteogenic and angiogenic markers were evaluated by RT-qPCR, Western blotting, and immunofluorescence. M1 macrophage phenotype was analyzed by flow cytometry. Osteogenesis was examined by histological staining, and angiogenic capacity was assessed using functional assays. <b>Results:</b> The present study found that simvastatin decreased M1 macrophage markers (CD86) and stimulated M1 macrophages to express high levels of pro-regenerative cytokines (BMP-2 and VEGF). In addition, simvastatin promoted osteogenic differentiation in MC3T3-E1 cells and angiogenic gene expression in HUVECs. Importantly, simvastatin enhanced the osteogenic capacity of MC3T3-E1 and the angiogenic potential of HUVECs by inhibiting M1 macrophage polarization in vitro. <b>Conclusions:</b> We demonstrated that simvastatin could confer favorable bone immunomodulatory properties and influence the crosstalk behavior between immune cells and osteoblasts and vascular endothelial cells to promote bone healing. |
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| institution | Kabale University |
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| spelling | doaj-art-7e399a45d9b949838db0a0fefd3501912025-08-20T03:27:15ZengMDPI AGBiomedicines2227-90592025-06-01136145410.3390/biomedicines13061454The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and AngiogenesisSiyu Zhu0Yunmeng Tong1Jiaqian Huang2Yuzhu He3Wenqi Fu4Yaran Zang5Huiying Liu6School of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, ChinaSchool of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, ChinaSchool of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, ChinaSchool of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, ChinaSchool of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, ChinaSchool of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, ChinaSchool of Stomatology, Dalian Medical University, No. 9 West Section, Lvshun South Road, Dalian 116044, China<b>Background:</b> The immune response is essential for bone regeneration, and macrophages in the immune microenvironment contribute to bone metabolism and angiogenesis. Emerging evidence demonstrates that simvastatin is a promising candidate for bone repair and promotes bone formation both in vitro and in vivo. However, the effect of simvastatin on macrophages and the following outcomes are still unclear. <b>Objectives:</b> This study aimed to investigate the potential immunomodulatory effect of simvastatin on M1 macrophages and its subsequent impact on osteogenesis and angiogenesis. <b>Methods:</b> Cell viability was assessed by CCK-8. Osteogenic and angiogenic markers were evaluated by RT-qPCR, Western blotting, and immunofluorescence. M1 macrophage phenotype was analyzed by flow cytometry. Osteogenesis was examined by histological staining, and angiogenic capacity was assessed using functional assays. <b>Results:</b> The present study found that simvastatin decreased M1 macrophage markers (CD86) and stimulated M1 macrophages to express high levels of pro-regenerative cytokines (BMP-2 and VEGF). In addition, simvastatin promoted osteogenic differentiation in MC3T3-E1 cells and angiogenic gene expression in HUVECs. Importantly, simvastatin enhanced the osteogenic capacity of MC3T3-E1 and the angiogenic potential of HUVECs by inhibiting M1 macrophage polarization in vitro. <b>Conclusions:</b> We demonstrated that simvastatin could confer favorable bone immunomodulatory properties and influence the crosstalk behavior between immune cells and osteoblasts and vascular endothelial cells to promote bone healing.https://www.mdpi.com/2227-9059/13/6/1454simvastatinosteogenesisangiogenesismacrophage polarizationbone immune |
| spellingShingle | Siyu Zhu Yunmeng Tong Jiaqian Huang Yuzhu He Wenqi Fu Yaran Zang Huiying Liu The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis Biomedicines simvastatin osteogenesis angiogenesis macrophage polarization bone immune |
| title | The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis |
| title_full | The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis |
| title_fullStr | The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis |
| title_full_unstemmed | The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis |
| title_short | The Mechanism of Simvastatin-Mediated M1 Macrophage Polarization Contributing to Osteogenesis and Angiogenesis |
| title_sort | mechanism of simvastatin mediated m1 macrophage polarization contributing to osteogenesis and angiogenesis |
| topic | simvastatin osteogenesis angiogenesis macrophage polarization bone immune |
| url | https://www.mdpi.com/2227-9059/13/6/1454 |
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