NF-κB/let-7f-5p/IL-10 pathway involves in wear particle-induced osteolysis by inducing M1 macrophage polarization

Abstract

NF-κB signaling pathway shows significant influence on wear particle-induced osteolysis, and this study aims to explore the underlying mechanism and the role of let-7f-5p in this process. A mouse calvarial osteolysis model was constructed with PMMA particles, and the bone marrow-derived macrophages (BMMs) were isolated from the osteolysis area. The expression of miRNA and protein was determined by qRT-PCR and western blot, respectively. The level of cytokines was evaluated with ELISA. Recombinant plasmids were transfected into cells for the endogenous expression of related genes. Dual-luciferase reporter assay was performed to determine the interaction between let-7f-5p and IL-10 in macrophage RAW264.7 cells. M1 macrophage polarization and expression of let-7f-5p were promoted in BMMs of osteolysis mouse model, compared with that in sham group. The expression of let-7f-5p was increased in the process of M1 macrophage polarization that induced by PMMA. Let-7f-5p was involved in M1 polarization in macrophages that treated with PMMA. IL-10 was negatively regulated by let-7f-5p. NF-κB regulated the expression of IL-10 through let-7f-5p. NF-κB participated in the PMMA-induced M1 macrophage polarization through let-7f-5p. Let-7f-5p contributed to PMMA-induced osteolysis by promoting M1 polarization of macrophages. The NF-κB/let-7f-5p/IL-10 pathway induces M1 macrophage polarization, and thus contributing to wear particle-induced osteolysis.