Abstract
BackgroundType II diabetes mellitus (T2DM) is an important risk factor for osseointegration of implants. The aim of this study was to explore key genes of T2DM affecting bone metabolism through bioinformatic analysis of published RNA sequencing data, identify potential biomarkers, and provide a reference for finding the molecular mechanism of abnormal osseointegration caused by T2DM.MethodsWe identified differentially expressed mRNAs and miRNAs from the Gene Expression Omnibus database using the R package ‘limma’ and analysed the predicted target genes using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and Gene Ontology analysis. At the same time, miRNA–mRNA interactions were explored using miRWalk 2.0.ResultsWe constructed an miRNA-gene regulatory network and a protein–protein interaction network. The enrichment pathways of differentially expressed mRNAs included extracellular matrix receptor interactions, protein digestion and absorption, the PI3K-Akt signalling pathway, cytokine–cytokine receptor interactions, chemokine signalling pathways, and haematopoietic cell lineage functions. We analysed the expression of these differentially expressed mRNAs and miRNAs in T2DM rats and normal rats with bone implants and identified Smpd3, Itga10, and rno-mir-207 as possible key players in osseointegration in T2DM.ConclusionSmpd3, Itga10, and rno-mir-207 are possible biomarkers of osseointegration in T2DM. This study sheds light on the possible molecular mechanism of abnormal osseointegration caused by bone metabolism disorder in T2DM.
Highlights
Type II diabetes mellitus (T2DM) is an important risk factor for osseointegration of implants
Recent studies have confirmed that miRNAs can inhibit Messenger RNA (mRNA) expression or reduce mRNA stability by binding to the 3′-untranslated regions of target mRNAs, regulating the expression of related genes. miRNAs play an important role in cell proliferation, differentiation, and apoptosis, and some studies have confirmed that several miRNAs are involved in osteogenic differentiation and bone metabolism-related diseases that affect bone tissue remodelling and new bone formation [15,16,17,18]
In the kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis of the GSE76364 dataset, extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, and the Phosphatidylinositol 3-kinase (PI3K)-Akt signalling pathway were enriched in downregulated differentially expressed (DE) mRNAs
Summary
Type II diabetes mellitus (T2DM) is an important risk factor for osseointegration of implants. Several studies have shown that microRNAs (miRNAs) play an important role in the occurrence and development of bone tissue remodelling around dental implants [11,12,13,14]. MiRNAs play an important role in cell proliferation, differentiation, and apoptosis, and some studies have confirmed that several miRNAs are involved in osteogenic differentiation and bone metabolism-related diseases that affect bone tissue remodelling and new bone formation [15,16,17,18] Recent studies have confirmed that miRNAs can inhibit mRNA expression or reduce mRNA stability by binding to the 3′-untranslated regions of target mRNAs, regulating the expression of related genes. miRNAs play an important role in cell proliferation, differentiation, and apoptosis, and some studies have confirmed that several miRNAs are involved in osteogenic differentiation and bone metabolism-related diseases that affect bone tissue remodelling and new bone formation [15,16,17,18]
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