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

Vrščaj, Lucija Ana; Marc, Janja; Ostanek, Barbara

doi:10.3390/genes13081443

Cited by 4 publications

(3 citation statements)

References 64 publications

(71 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The initial selection of miRNAs influenced by PTH was based on our previously published article ( 47 ), but for the current analysis only studies that were performed on osteoblasts were selected. These studies are compiled in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Towards an enhanced understanding of osteoanabolic effects of PTH-induced microRNAs on osteoblasts using a bioinformatic approach

Vrščaj,

Marc,

Ostanek

2024

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

In this study, we used a bioinformatic approach to construct a miRNA-target gene interaction network potentially involved in the anabolic effect of parathyroid hormone analogue teriparatide [PTH (1–34)] on osteoblasts. We extracted a dataset of 26 microRNAs (miRNAs) from previously published studies and predicted miRNA target interactions (MTIs) using four software tools: DIANA, miRWalk, miRDB, and TargetScan. By constructing an interactome of PTH-regulated miRNAs and their predicted target genes, we elucidated signaling pathways regulating pluripotency of stem cells, the Hippo signaling pathway, and the TGF-beta signaling pathway as the most significant pathways in the effects of PTH on osteoblasts. Furthermore, we constructed intersection of MTI networks for these three pathways and added validated interactions. There are 8 genes present in all three selected pathways and a set of 18 miRNAs are predicted to target these genes, according to literature data. The most important genes in all three pathways were BMPR1A, BMPR2 and SMAD2 having the most interactions with miRNAs. Among these miRNAs, only miR-146a-5p and miR-346 have validated interactions in these pathways and were shown to be important regulators of these pathways. In addition, we also propose miR-551b-5p and miR-338–5p for further experimental validation, as they have been predicted to target important genes in these pathways but none of their target interactions have yet been verified. Our wet-lab experiment on miRNAs differentially expressed between PTH (1–34) treated and untreated mesenchymal stem cells supports miR-186–5p from the literature obtained data as another prominent miRNA. The meticulous selection of miRNAs outlined will significantly support and guide future research aimed at discovering and understanding the crucial pathways of osteoanabolic PTH-epigenetic effects on osteoblasts. Additionally, they hold potential for the discovery of new PTH target genes, innovative biomarkers for the effectiveness and safety of osteoporosis-affected treatment, as well as novel therapeutic targets.

show abstract

Section: Resultsmentioning

confidence: 99%

Towards an enhanced understanding of osteoanabolic effects of PTH-induced microRNAs on osteoblasts using a bioinformatic approach

Vrščaj,

Marc,

Ostanek

2024

Front. Endocrinol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Antiresorptive treatment with denosumab induced changes in circulating miRNAs and, as would be expected, the response was most pronounced in the subgroup of patients previously treated with anabolic teriparatide [ 125 ]. An in silico study suggests that the effect of teriparatide on genes is most likely mediated by miR-146a-5p, miR-205-3p, miR-33a-3p, miR-338-5p and miR-410-3p [ 126 ].…”

Section: Circulating Mirnas As Biomarkers In Metabolic Diseasementioning

confidence: 99%

MicroRNAs: emerging biomarkers and therapeutic targets of bone fragility in chronic kidney disease

Smout

Craenenbroeck

Jørgensen

et al. 2022

Clinical Kidney Journal

View full text Add to dashboard Cite

Bone fragility is highly prevalent, yet underdiagnosed in patients with chronic kidney disease (CKD). Incomplete understanding of the pathophysiology and limitations of current diagnostics contribute to therapeutic hesitation, if not nihilism. This narrative review addresses the question whether miRNAs may improve therapeutic decision making in osteoporosis and renal osteodystrophy. MicroRNAs are key epigenetic regulators of bone homeostasis and show promise both as therapeutic targets and as biomarkers, primarily of bone turnover. Experimental studies show that miRNAs are involved in several osteogenic pathways. Clinical studies exploring the usefulness of circulating miRNAs for fracture risk stratification and for guiding and monitoring therapy are few and, so far, provide inconclusive results. Likely, (pre)analytical heterogeneity contributes to these equivocal results. In conclusion, miRNAs are promising in metabolic bone disease, both as a diagnostic tool and as therapeutic targets, but not yet ready for clinical prime time.

show abstract

“…On the other hand, epigenetic factors are thought to play an important role in complex disorders, and therefore their role in type 1 diabetes [ 9 ] and osteoporosis [ 10 ] is reviewed in detail. Moreover, the presented interactome of PTH-regulated miRNAs and their predicted target genes may facilitate further understanding of the mechanism of action of PTH on bone metabolism and the development of new therapeutic targets.…”

mentioning

confidence: 99%

Special Issue “Genetics and Epigenetics in Endocrine Disorders”

Trebušak Podkrajšek,

Kotnik

2023

Genes

View full text Add to dashboard Cite

show abstract

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

Cited by 4 publications

References 64 publications

Towards an enhanced understanding of osteoanabolic effects of PTH-induced microRNAs on osteoblasts using a bioinformatic approach

Towards an enhanced understanding of osteoanabolic effects of PTH-induced microRNAs on osteoblasts using a bioinformatic approach

MicroRNAs: emerging biomarkers and therapeutic targets of bone fragility in chronic kidney disease

Special Issue “Genetics and Epigenetics in Endocrine Disorders”

Contact Info

Product

Resources

About