IL-34 Regulates Macrophage Polarization and Bone Defect Healing in Aged Mice

Area of Science:

• Immunology
• Orthopedics
• Gerontology

Background:

• Aging significantly compromises bone-defect healing, primarily due to immune microenvironment dysregulation and macrophage dysfunction.
• Interleukin-34 (IL-34) is vital for macrophage biology, but its specific role in age-related bone healing deficits is not well understood.

Purpose of the Study:

• To investigate the role and mechanism of IL-34 in aging-impaired tibial bone-defect healing in mice.
• To determine if IL-34 can serve as a therapeutic target for improving bone repair in aged individuals.

Main Methods:

• Tibial bone defect model in young and aged C57BL/6 mice.
• Microcomputed tomography, histological staining, flow cytometry, RNA sequencing, and in vitro cell experiments.
• Analysis of IL-34 expression, macrophage infiltration, and M2 polarization.

Main Results:

• Aging markedly reduced bone mass, osteogenic differentiation, and bone defect healing.
• Aged mice exhibited decreased macrophage numbers and suppressed M2 polarization at bone defect sites.
• IL-34 expression and secretion were downregulated in aged mice, correlating with impaired macrophage proliferation and M2 polarization.

Conclusions:

• Aging impairs tibial bone healing by downregulating IL-34, reducing macrophage infiltration, and inhibiting M2 polarization.
• IL-34 promotes bone healing by regulating macrophage function, indicating its potential as a therapeutic target for age-related bone repair.