Analysis of the effect of zoledronic acid on gene differences in rat jaw

Abstract

BackgroundWith the widespread use of bisphosphonates, there are more and more complications about bisphosphonates, bisphosphonate-related osteonecrosis of the jaw is one.In the past ten years, there have been many studies on the mechanism of bisphosphonate associated jaw necrosis. ObjectiveTo investigate the influence and analysis of zoledronic acid on gene differences in rat jaw. MethodsSix Sprague-Dawley female rats were randomly divided into control group (n = 3) and experimental group (n = 3). The experimental group received zoledronic acid injection for 12 weeks (dose of 0.2 mg / kg, 3 times a week).Control groups were injected with normal saline for 12 weeks. All rats were subjected to left mandibular first molar extraction 12 weeks later.After 8 weeks of tooth extraction, all rats were sacrificed and the mandible was removed.RNA-seq was used to analyze differential gene changes in all mandibles. Bioinformatics analysis of differential genes. ResultsCompared with the two rat groups, there were 2,830 different genes, including 1,001 upregulated genes and 1,829 down-regulated genes. Gene Ontology analysis revealed that the upregulated genes were mainly associated with immune-related pathways. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that Hedgehog signaling pathway, Notch signaling pathway and Hippo signaling pathway were associated with upregulated genes. After the Gene Set Enrichment Analysis, the Gene Ontology analysis showed that 2559 / 6588 gene sets are upregulated in phenotype experimental group,and 342 gene sets with p <0.05. The Kyoto Encyclopedia of Genes and Genomes analysis revealed that 95 / 316 gene sets are upregulated in phenotype experimental group, and four gene sets(Notch pathway, other types of O-glycan biosynthesis, ovarian steridogenesis and Hippo pathway) with p <0.05. ConclusionsChanges in differential genes are mainly related to immune-related processes and pathways, and pathways related to bone metabolism. The up-regulation of some genes can promote the progress of Bisphosphonate-related osteonecrosis of the jaw.