Bone remodeling is a coordinated process of coupled bone resorption and formation in which Wnt signaling pathway and the RANK/RANK/OPG signaling pathway play an important role. Parathyroid hormone (PTH) is a hormone that affects bone formation and resorption. In the case of intermittent exposure, there is an increase in bone mass, so its recombinant form (teriparatide) is used in the treatment of osteoporosis as an osteoanabolic drug. Changes of micro RNA (miRNA) expression represent one of the mechanisms of PTH action on bone. MiRNAs are small non-coding RNA molecules that inhibit gene expression after transcription.
The aim of the master's thesis was to find miRNAs regulated by PTH, which are involved in the Wnt signaling pathway or RANK/RANKL/OPG pathway.
Literature search was performed in the electronic library PubMed, followed by target predictions for the identified miRNAs with bioinformatics tools DIANA tools, miRWalk, TargetScan and miRDB. Experimentally confirmed interactions were identified with the bioinformatics tool miRTarBase and interactomes drawn with Cytoscape.
Literature review resulted in 17 relevant articles, with a set of 69 miRNAs for which predictions were made. The total number of all target genes was 12782 and 477 were experimentally confirmed. Next, we undertook the analysis of miRNAs, which have the potential to influence the Wnt signaling pathway, RANK/RANKL/OPG signaling pathway or both. MiRNA that affects both signaling pathways can represent a promising potential therapeutic, as long as its silencing effects are appropriate, so it acts as an osteoanabolic and antiresorptive. As a potential therapeutic for the treatment of osteoporosis, miRNA hsa-miR-24-2-5p could be used, the expression of which in bone cells should be measured in the following studies.
Our results confirm the significant influence of miRNA on both signaling pathways and represent a starting point for development of new active substances in the treatment of osteoporosis.
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