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.

Abstract

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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