Interactome of PTH-Regulated miRNAs and Their Predicted Target Genes for Investigating the Epigenetic Effects of PTH (1–34) in Bone Metabolism

Abstract

Osteoporosis is a metabolic bone disease that mostly affects the elderly. A lot of drugs are available, mostly with an antiresorptive effect but just a few with an osteoanabolic effect, meaning they promote bone building. PTH (1-34) or teriparatide is an osteoanabolic drug, but its efficacy varies between individuals. We performed a literature review and extracted a dataset of 62 microRNAs (miRNAs) from 10 different studies; predicted miRNA target interactions (MTIs) were obtained with the help of four software tools: DIANA, miRWalk, miRDB and TargetScan. With the construction of an interactome of PTH-regulated miRNAs and their predicted target genes, we elucidated miR-146a-5p, miR-551b-5p, miR-205-3p, miR-33a-3p, miR-338-5p as miRNAs with the most interactions and miR-410-3p as the miRNA targeting bone-related pathways with the highest significance. These miRNAs could help in further understanding the mechanism of action of PTH on bone metabolism and osteoporosis. They also have the potential for novel network-based biomarkers for osteoporosis treatment efficacy and safety and as new therapeutic targets.