miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration
Abstract Background Distraction osteogenesis (DO) is a highly effective method for bone regeneration. However, its prolonged treatment duration limits its clinical application. Parathyroid hormone (PTH) can promote distraction osteogenesis, but the underlying mechanism remains unclear. During distra...
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BMC
2025-05-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-02683-4 |
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| author | Yongdi Li Liyue Tian Zhishan Yang Yiheng Liu Duchenhui Li Zhenglong Tang |
| author_facet | Yongdi Li Liyue Tian Zhishan Yang Yiheng Liu Duchenhui Li Zhenglong Tang |
| author_sort | Yongdi Li |
| collection | DOAJ |
| description | Abstract Background Distraction osteogenesis (DO) is a highly effective method for bone regeneration. However, its prolonged treatment duration limits its clinical application. Parathyroid hormone (PTH) can promote distraction osteogenesis, but the underlying mechanism remains unclear. During distraction osteogenesis, macrophages modulate inflammation after phenotypic transition, promoting bone regeneration. PTH is known to affect the expression of specific miRNAs, and miR-155 has been shown to regulate macrophage polarization, with subsequent effects on inflammation. We hypothesized that miR-155 may participate in the osteogenic effect of PTH by regulating macrophage polarization. In this study, we aim to explored the mechanism by which PTH promotes distraction osteogenesis using both in vivo and in vitro models. Methods Established a rabbit model of mandibular distraction osteogenesis in which histomorphological observations confirmed the osteogenic effects of PTH and the reduced expression of miR-155. In addition, a lipopolysaccharide (LPS)-induced macrophage distraction model was established. ELISA was used to measure the expression of the inflammatory cytokines TNF-α and IL-1β in animal serum and cell supernatants. RT‒qPCR was used to detect the expression of miR-155 and SOCS1, and Western blotting and IHC were used to examine SOCS1 expression and explore its mechanisms. The overexpression of miR-155, the proportion of M1 macrophages was reassessed, and the expressions of SOCS1, TNF-α, and IL-1β were concurrently evaluated. Results PTH administration significantly downregulated miR-155 expression in both the rabbit model and in vitro macrophages. This led to an upregulation of SOCS1 expression, which in turn reduced the polarization of M1 macrophages. The levels of TNF-α and IL-1β were also markedly reduced in the PTH-treated groups compared to the control groups. In the distraction zone, histological analysis revealed that the experimental group had better trabecular bone formation, with higher density and maturity of trabeculae compared to the control group. Flow cytometry analysis showed a significant reduction in the proportion of M1 macrophages in PTH-treated cells. The dual-luciferase reporter assay confirmed that miR-155 directly targets SOCS1. Conclusions PTH downregulates miR-155 in new bone and macrophages during mandibular DO, increasing SOCS1 expression, reducing M1 macrophages, and enhancing bone regeneration by lowering inflammation. |
| format | Article |
| id | doaj-art-ea7362261b574958aa218e13124a5e8c |
| institution | DOAJ |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-ea7362261b574958aa218e13124a5e8c2025-08-20T03:16:52ZengBMCEuropean Journal of Medical Research2047-783X2025-05-0130111210.1186/s40001-025-02683-4miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administrationYongdi Li0Liyue Tian1Zhishan Yang2Yiheng Liu3Duchenhui Li4Zhenglong Tang5School of Basic Sciences, Guizhou Medical UniversityDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Guizhou Medical UniversityDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Guizhou Medical UniversityDepartment of Oral and Maxillofacial Surgery, School of Stomatology, Guizhou Medical UniversitySchool of Basic Sciences, Guizhou Medical UniversitySchool of Basic Sciences, Guizhou Medical UniversityAbstract Background Distraction osteogenesis (DO) is a highly effective method for bone regeneration. However, its prolonged treatment duration limits its clinical application. Parathyroid hormone (PTH) can promote distraction osteogenesis, but the underlying mechanism remains unclear. During distraction osteogenesis, macrophages modulate inflammation after phenotypic transition, promoting bone regeneration. PTH is known to affect the expression of specific miRNAs, and miR-155 has been shown to regulate macrophage polarization, with subsequent effects on inflammation. We hypothesized that miR-155 may participate in the osteogenic effect of PTH by regulating macrophage polarization. In this study, we aim to explored the mechanism by which PTH promotes distraction osteogenesis using both in vivo and in vitro models. Methods Established a rabbit model of mandibular distraction osteogenesis in which histomorphological observations confirmed the osteogenic effects of PTH and the reduced expression of miR-155. In addition, a lipopolysaccharide (LPS)-induced macrophage distraction model was established. ELISA was used to measure the expression of the inflammatory cytokines TNF-α and IL-1β in animal serum and cell supernatants. RT‒qPCR was used to detect the expression of miR-155 and SOCS1, and Western blotting and IHC were used to examine SOCS1 expression and explore its mechanisms. The overexpression of miR-155, the proportion of M1 macrophages was reassessed, and the expressions of SOCS1, TNF-α, and IL-1β were concurrently evaluated. Results PTH administration significantly downregulated miR-155 expression in both the rabbit model and in vitro macrophages. This led to an upregulation of SOCS1 expression, which in turn reduced the polarization of M1 macrophages. The levels of TNF-α and IL-1β were also markedly reduced in the PTH-treated groups compared to the control groups. In the distraction zone, histological analysis revealed that the experimental group had better trabecular bone formation, with higher density and maturity of trabeculae compared to the control group. Flow cytometry analysis showed a significant reduction in the proportion of M1 macrophages in PTH-treated cells. The dual-luciferase reporter assay confirmed that miR-155 directly targets SOCS1. Conclusions PTH downregulates miR-155 in new bone and macrophages during mandibular DO, increasing SOCS1 expression, reducing M1 macrophages, and enhancing bone regeneration by lowering inflammation.https://doi.org/10.1186/s40001-025-02683-4Parathyroid hormoneDistraction osteogenesisMiR-155Macrophage |
| spellingShingle | Yongdi Li Liyue Tian Zhishan Yang Yiheng Liu Duchenhui Li Zhenglong Tang miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration European Journal of Medical Research Parathyroid hormone Distraction osteogenesis MiR-155 Macrophage |
| title | miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration |
| title_full | miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration |
| title_fullStr | miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration |
| title_full_unstemmed | miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration |
| title_short | miR-155 targets SOCS1 to modulate the phenotype transition of M1 macrophage in distraction osteogenesis promoted by PTH administration |
| title_sort | mir 155 targets socs1 to modulate the phenotype transition of m1 macrophage in distraction osteogenesis promoted by pth administration |
| topic | Parathyroid hormone Distraction osteogenesis MiR-155 Macrophage |
| url | https://doi.org/10.1186/s40001-025-02683-4 |
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