1. Urolithin B inhibits the differentiation of M1 macrophages and relieves the inflammation around the implants under osteoporosis via down-regulating the phosphorylation of VEGFR2.
- Author
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Xiao L, Yang Y, Yu J, Li Y, Chen S, Gu Y, Tang C, Yang H, Wang Z, and Geng D
- Subjects
- Animals, Female, Mice, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Disease Models, Animal, Down-Regulation drug effects, Inflammation drug therapy, Mice, Inbred C57BL, Osseointegration drug effects, Phosphorylation drug effects, Prostheses and Implants, RAW 264.7 Cells, Cell Differentiation drug effects, Coumarins pharmacology, Coumarins therapeutic use, Macrophages immunology, Macrophages drug effects, Macrophages metabolism, Osteoporosis drug therapy, Osteoporosis immunology, Vascular Endothelial Growth Factor Receptor-2 metabolism
- Abstract
The inflammation causes the destroyed osseointegration at the implant-bone interface, significantly increasing the probability of implant loosening in osteoporotic patients. Currently, inhibiting the differentiation of M1 macrophages and the inflammatory response could be a solution to stabilize the microenvironment of implants. Interestingly, some natural products have anti-inflammatory and anti-polarization effects, which could be a promising candidate for stabilizing the implants' microenvironment in osteoporotic patients. This research aims to explore the inhibitory effect of Urolithin B(UB) on macrophage M1 polarization, which 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, RAW264.7 cells were polarized to M1 macrophages using lipopolysaccharide (LPS) and analyzed by immunofluorescence (IF) staining, Western blot (WB), and flow cytometry. The CSP100 plus chip experiments were used to explore the potential mechanisms behind the inhibiting effects of UB. Through observation of these experiments, UB can improve the osseointegration between the implants and femurs in osteoporotic mice and enhance the stability of implants. The UB can inhibit the differentiation of M1 macrophages and local inflammation via inhibiting the phosphorylation of VEGFR2, which can be further proved by the weakened inhibited effects of UB in macrophages with lentivirus-induced overexpression of VEGFR2. Overall, UB can specifically inhibit the activation of VEGFR2, alleviate local inflammation, and improve the stability of implants in osteoporotic mice., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)
- Published
- 2024
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