IL-17A reduces the biological activity of Masquelet-induced membranes by inhibiting the expression of matrix metalloproteinases
Objective To explore the signaling mechanism of Masquelet-induced reduction in membrane angiogenesis and decreased biological activity.Methods A rat femoral critical bone defect model was established using Kirschner wire internal fixation.After successful modeling,induced membrane samples were taken out at 2,4,6,and 8 weeks postoperatively for biological detection and proteomic analysis.Immunohistochemical methods were used to detect the number of induced membrane CD31+blood vessels.GO enrichment was used to analyze the biological process of induced membrane activity reduction.KEGG enrichment was used to analyze the signaling pathways of induced membrane activity reduction.Western blot was used to detect the protein expression levels of induced membrane IL-7A,MMP8,MMP9,and MMP13.Results CD31 immunohistochemistry showed that at 2 and 4 weeks,there was more induced membrane angiogenesis and better biological activity.After 4 weeks,blood vessels gradually decrease and biological activity decreases.GO enrichment analyzed the collagen degradation metabolism process which was related to decreased induced membrane biological activity,which includes proteins of the matrix metalloproteinase family:MMP8,MMP9,MMP13.KEGG enrichment analysis showed that MMP9 and MMP13 were downstream regulatory factors of IL-17A in the IL-17A signaling pathway,and the IL-17A signaling pathway was in the top 20 pathway that decreased induced membrane activity.Western blot results confirmed that IL-17A,MMP8,MMP9,and MMP13 were all expressed in the induced membrane at different time points,and the decrease at 8 weeks was statistically significant compared to 4 weeks.Conclusion The decreased expression of IL-17A signaling pathway and its downstream MMP8,MMP9,and MMP13 is a key factor in induced membrane decreased angiogenesis and biological activity.
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