Piezo1 promotes M1 macrophage polarization and impairs osteogenic differentiation in bone infection

BACKGROUND: Bone infection induces a strong inflammatory response and leads to impaired bone regeneration, in which macrophages sense mechanistic signals and modulate immune responses in the inflammatory microenvironment through Piezo1. Nonetheless, the regulatory role of Piezo1 in macrophages during bone infection remains elusive. METHODS: Rat models of infected bone defects were established for bulk RNA sequencing and single-cell RNA sequencing. Tissues were collected from infected human bones and infected bone marrow cavity tissues of rats for in vivo validation. Indirect co-culture cell experiments were conducted using mouse mononuclear macrophages and mouse bone marrow mesenchymal stem cells for in virto validation. RESULTS: Piezo1 was upregulated in bone marrow macrophages during infection, driving M1 polarization and inflammatory cytokine secretion, which triggered PANoptosis and impaired the osteogenic differentiation of bone marrow mesenchymal stem cells. Piezo1 inhibition attenuated these effects, confirming its regulatory role. CONCLUSIONS: Within the inflammatory microenvironment during infection, Piezo1 expression is increased in macrophages and mediates macrophage polarization toward M1 and pro-inflammatory cytokine secretion, inducing PANoptosis and impairing osteogenic differentiation in bone marrow mesenchymal stem cells. Targeting Piezo1-mediated crosstalk between macrophages and bone marrow mesenchymal stem cells offers a novel strategy for restoring bone regeneration in bone infection.