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Updated: Nov 19, 2025

Polarization and Characterization of M1 and M2 Human Monocyte-Derived Macrophages on Implant Surfaces
Published on: December 6, 2024
MicroRNA-125a-5p modulates macrophage polarization by targeting E26 transformation-specific variant 6 gene during
Wendan He1, Nan Zhang2, Zhengshen Lin3
1Department of Stomatology, Shenzhen Hospital, Southern Medical University, Shenzhen, 518033, China.
Objective:
The aim of this study was to investigate the role of microRNA-125a-5p (miR-125a-5p) in macrophages during orthodontic tooth movement (OTM).
Design:
Periodontal ligament tissues were collected from patients underwent OTM. Periodontal ligament cells were isolated from periodontal ligament tissues. Periodontal ligament stem cells were isolated from normal human impacted third molars. The miR-125-5p levels were measured by real-time quantitative polymerase chain reaction. The impact of miR-125-5p on macrophage polarization was tested by alizarin red staining assay. The effects of miR-125-5p and E26 transformation-specific variant 6 gene (ETV6) on M1/M2 macrophages phenotype markers were determined by real-time quantitative polymerase chain reaction, western blot, and flow cytometry analyses. The interaction between miR-125-5p and ETV6 was verified using luciferase reporter and RNA immunoprecipitation assays.
Results:
Periodontal miR-125a-5p was upregulated under the force. Macrophage polarization facilitated osteogenesis by cocultured system. Moreover, miR-125a-5p was upregulated in macrophages polarized with M2 conditions. MiR-125a-5p downregulation promoted the expression of M1 phenotype markers, while suppressed the expression of M2 markers. Mechanistically, ETV6 was confirmed to be a target of miR-125a-5p. ETV6 overexpression increased the expression of M1 polarized markers, while decreased the expression of M2 polarized markers. Furthermore, ETV6 knockdown reversed the effects of miR-125a-5p inhibitor on both M1 macrophages and M2 macrophages.
Conclusions:
Overall, miR-125a-5p facilitates bone healing by targeting ETV6 to promote macrophage M2 polarization.
Insights
MicroRNA-125a-5p promotes bone healing during orthodontic tooth movement by enhancing M2 macrophage polarization. This involves targeting the ETV6 gene, crucial for regulating macrophage phenotypes and facilitating tissue repair.
Area of Science:
- Molecular Biology
- Immunology
- Orthodontics
Background:
- Orthodontic tooth movement (OTM) involves complex cellular and molecular processes in the periodontal ligament.
- Macrophage polarization plays a critical role in modulating inflammatory responses and tissue remodeling during OTM.
- The specific role of microRNA-125a-5p (miR-125a-5p) in macrophage behavior during OTM remains largely unexplored.
Purpose of the Study:
- To investigate the role of miR-125a-5p in macrophages during the process of orthodontic tooth movement.
- To elucidate the molecular mechanisms by which miR-125a-5p influences macrophage polarization.
- To determine the therapeutic potential of targeting miR-125a-5p for enhancing bone healing in OTM.
Main Methods:
- Isolation and culture of periodontal ligament cells and stem cells from human tissues.
- Quantification of miR-125a-5p levels using real-time quantitative PCR.
- Assessment of macrophage polarization (M1/M2) using alizarin red staining, flow cytometry, Western blot, and gene expression analysis.
- Verification of the interaction between miR-125a-5p and its target gene ETV6 using luciferase reporter and RNA immunoprecipitation assays.
Main Results:
- miR-125a-5p expression was significantly upregulated in periodontal tissues under orthodontic force and in M2-polarized macrophages.
- Downregulation of miR-125a-5p promoted M1 macrophage markers while suppressing M2 markers.
- ETV6 was identified as a direct target of miR-125a-5p; ETV6 overexpression mimicked the effects of miR-125a-5p inhibition on macrophage polarization.
Conclusions:
- miR-125a-5p plays a crucial role in promoting M2 macrophage polarization during orthodontic tooth movement.
- The mechanism involves miR-125a-5p targeting ETV6, thereby influencing macrophage phenotype.
- These findings suggest that miR-125a-5p is a potential therapeutic target for enhancing bone healing in orthodontic treatments.
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