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

Background: With 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. Objective: To investigate the influence and analysis of zoledronic acid on gene differences in rat jaw. Methods: Six 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. Bio-informatics analysis of differential genes. Results: Compared 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 signal-ing 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. Conclusions: Changes 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. (c) 2022 Elsevier Masson SAS. All rights reserved.