Avicularin alleviates osteoporosis-induced implant loosening by attenuating macrophage M1 polarization via its inhibitory effect on the activation of NF-κB.

Currently, the failure rate for internal fixation in patients with osteoporosis can be reduced by antiosteoporosis therapy alone. However, the administration of anti-osteoporotic drugs is not a complete solution. Therefore, it is necessary to investigate other causes of surgical failure, such as inflammation. In recent years, the inflammation caused by macrophage M1 polarization has garnered wide attention. The purpose of this research is to explore the inhibitory effect of avicularin (AL) on macrophage M1 polarization, by which it ameliorates inflammation, thus alleviating implant instability. We established an osteoporosis mouse model of implant loosening. The mouse tissues were taken out for morphological analysis, staining analysis and bone metabolic index analysis. In in vitro experiments, bone marrow derived macrophages (BMDM) and RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS), and analyzed by immunofluorescence (IF) staining, Western blot (WB) and flow cytometry. WB was also used to analyze the nuclear factor kappa-B (NF-κB) pathway. In addition, the expression levels of inflammatory cytokines were detected in cell supernatant using ELISA kits. Through observation of this experiments, we found that AL can inhibit M1 polarization of macrophages. Moreover, it can significantly inhibit the release of inflammatory factors to improve multiple mouse femur parameters. Furthermore, AL inhibited the phosphorylation of IKBα and P65 in the NF-κB pathway. The above data indicate that AL ameliorates inflammatory responses by inhibiting macrophage M1 polarization via its inhibitory effect on the NF-κB pathway, thus alleviating the instability of implants in mice with osteoporosis.