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.

NF-κB/TWIST1 Mediates Migration and Phagocytosis of Macrophages in the Mice Model of Implant-Associated Staphylococcus aureus Osteomyelitis

“…NF-κB is considered to be a member of pro-inflammatory family of main transcription factors in inflammatory processes. It participates in M1 macrophage polarization induced by various stimulations (Gao et al, 2018;Genard et al, 2018). Consistent with their reports, our data demonstrate that NF-κB pathway activation is associated with TWIST1 expression and M1 polarization in response to S. aureus infection.…”

Hypoxia-induced let-7f-5p/TARBP2 feedback loop regulates osteosarcoma cell proliferation and invasion by inhibiting the Wnt signaling pathway

“…Our study found that TARBP2 increases the expression of let-7f-5p in OS cells, suggesting that TARBP2 may promote the maturation of pre-let-7f in these cells. The let-7f-5p miRNA is a member of the let-7 family, which is involved in cell growth, migration, invasion, and angiogenesis in tumors [15][16][17]. In the present study, we showed that let-7f-5p targeted TARBP2, suggesting there was a regulatory feedback loop between let-7f-5p and TARBP2.…”

“…In the present study, we focused on let-7f-5p, which is located at 9q22.3 and is a member of let-7 family. let-7f has been shown to play an important role in cell growth, migration, invasion, and angiogenesis in tumors [15,16]. However, the molecular mechanism by which let-7f-5p regulates OS cell proliferation and invasion remains largely unknown.…”

<p>SIRT1 inhibits hepatocellular carcinoma metastasis by promoting M1 macrophage polarization via NF-&kappa;B pathway</p>

“…Because NF-κB pathways play an essential role in M1 macrophage polarization,27 our research investigated its impact on NF-κB stimulation. Phosphorylation of p65 as well as IκB kinase (IKK) was noticeably increased in SIRT1-transfected macrophages compared to vector-transfected macrophages after LPS+ IFN-γ treatment (Figure 5).…”