Comparative profiles of DNA methylation and differential gene expression in osteocytic areas from aged and young mice.

Abstract

Altered DNA methylation upon ageing may result in many age-related diseases such as osteoporosis. However, the changes in DNA methylation that occur in cortical bones, the major osteocytic areas, remain unknown. In our study, we extracted total DNA and RNA from the cortical bones of 6-month-old and 24-month-old mice and systematically analysed the differentially methylated regions (DMRs), differentially methylated promoters (DMPs) and differentially expressed genes (DEGs) between the mouse groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of the DMR-related genes revealed that they were mainly associated with metabolic signalling pathways, including glycolysis, fatty acid and amino acid metabolism. Other genes with DMRs were related to signalling pathways that regulate the growth and development of cells, including the PI3K-AKT, Ras and Rap1 signalling pathways. The gene expression profiles indicated that the DEGs were mainly involved in metabolic pathways and the PI3K-AKT signalling pathway, and the profiles were verified through real-time quantitative PCR (RT-qPCR). Due to the pivotal roles of the affected genes in maintaining bone homeostasis, we suspect that these changes may be key factors in age-related bone loss, either together or individually. Our study may provide a novel perspective for understanding the osteocyte and its relationship with osteoporosis during ageing. SIGNIFICANCE OF THE STUDY: Our study identified age-related changes in gene expressions in osteocytic areas through whole-genome bisulfite sequencing (WGBS) and RNA-seq, providing new theoretical foundations for the targeted treatment of senile osteoporosis.