Macrophages regulate angiogenesis-osteogenesis coupling induced by mechanical loading through the Piezo1 pathway.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Orthopedics

Background:

• Bone is a mechanosensitive tissue requiring cellular response to mechanical stimuli for regeneration.
• Macrophages play a vital role in bone formation, regeneration, and maintenance, but their mechanosensory mechanisms are not fully understood.
• Piezo1 channels are known mechanotransducers in various cell types, including macrophages.

Purpose of the Study:

• To investigate the role of Piezo1 in macrophage mechanotransduction during mechanical loading-induced bone regeneration.
• To elucidate how mechanical stimulation regulates macrophage activity and their contribution to bone repair.

Main Methods:

• Utilized conditional knockout (KO) of Piezo1 in LysM+ myeloid cells (macrophages).
• Applied in vivo mechanical loading to bone defect models in mice.
• Assessed macrophage polarization (CD206+), angiogenesis-osteogenesis coupling, cell proliferation, and bone regeneration.
• Transplanted wild-type (WT) bone marrow-derived macrophages into Piezo1 KO mice.

Main Results:

• Mechanical loading increased CD206+ macrophages, angiogenesis-osteogenesis coupling, and cell proliferation, enhancing bone regeneration.
• Conditional KO of Piezo1 in macrophages abolished these loading-induced enhancements.
• WT macrophage transplantation rescued mechanosensitive coupling and promoted bone regeneration in Piezo1 KO mice.

Conclusions:

• Piezo1 in macrophages is essential for mechanical loading-induced bone regeneration.
• Piezo1 mediates macrophage polarization to the CD206+ phenotype, facilitating angiogenesis-osteogenesis coupling and cell proliferation.
• Targeting Piezo1 in macrophages presents a potential strategy for enhancing bone repair.