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Updated: Jul 28, 2025

Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Macrophage MVP regulates fracture repair by promoting M2 polarization via JAK2-STAT6 pathway
Yan Yang1, Na Zhao1, Ruobing Wang1
1Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China; Department of Orthodontics, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, China.
Objective:
Major vault protein (MVP) is vital in various macrophage-related inflammatory diseases. However, the effects of MVP on macrophage polarization during fracture repair are still unknown.
Methods:
We used Mvpflox/floxLyz2-Cre mice (myeloid-specific MVP gene knockout, abbreviated as MacKO) and Mvpflox/flox (abbreviated as MacWT) mice to compare their fracture healing phenotype. Next, we traced the changes in macrophage immune status in vivo and in vitro. We further explored the effects of MVP on osteogenesis and osteoclastogenesis. Finally, we re-expressed MVP in MacKO mice to confirm the role of MVP in fracture healing.
Results:
The lack of MVP in macrophages impaired their transition from a pro-inflammatory to an anti-inflammatory phenotype during fracture repair. The increased secretion of pro-inflammatory cytokines by macrophages promoted their osteoclastic differentiation and impaired BMSC osteogenic differentiation, ultimately leading to impaired fracture repair in MacKO mice. Last, adeno-associated virus (AAV)-Mvp tibial injection significantly promoted fracture repair in MacKO mice.
Conclusions:
Our findings showed MVP has a previously unknown immunomodulatory role in macrophages during fracture repair. Targeting macrophage MVP may represent a novel therapeutic method for fracture treatment.
Insights
Major vault protein (MVP) is crucial for macrophage polarization during fracture repair. Its absence impairs healing by promoting inflammation and hindering bone formation, but targeting MVP can improve fracture outcomes.
Area of Science:
- Immunology
- Orthopedics
- Cell Biology
Background:
- Major vault protein (MVP) plays a role in macrophage-related inflammatory diseases.
- The function of MVP in macrophage polarization during fracture repair remains unclear.
Purpose of the Study:
- To investigate the role of MVP in macrophage polarization during fracture healing.
- To explore the impact of MVP on osteogenesis and osteoclastogenesis in the context of fracture repair.
Main Methods:
- Utilized myeloid-specific MVP knockout (MacKO) and wild-type (MacWT) mice to compare fracture healing.
- Assessed macrophage immune status in vivo and in vitro.
- Investigated MVP's effects on osteogenesis and osteoclastogenesis, with confirmation via MVP re-expression in MacKO mice.
Main Results:
- Macrophage-specific MVP deficiency disrupted the pro-inflammatory to anti-inflammatory transition during fracture repair.
- Lack of MVP led to increased pro-inflammatory cytokine secretion, enhanced osteoclast differentiation, and impaired bone marrow stromal cell (BMSC) osteogenic differentiation.
- Adeno-associated virus (AAV)-mediated MVP delivery to the tibia significantly improved fracture repair in MacKO mice.
Conclusions:
- MVP exhibits a novel immunomodulatory function in macrophages during fracture repair.
- Targeting macrophage MVP presents a potential therapeutic strategy for enhancing fracture healing.
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