Numerous experimental data shows crucial involvement of miRs in skeletal development in embryos, osteogenic differentiation, and maturation. However, molecular mechanisms of miRs action, in other words their target signaling pathways and transcriptional factors that specific drives osteogenic differentiation is far from being understood. With metaanalysis we identified miRs significantly involved in hMSCs osteogenic differentiation. Statistical analysis revealed significant trend of upregulation of let7a, mir21, mir26a, mir29b, mir101, mir143, mir218 during hMSCs differentiation into osteoblast. And the opposite trend was shown for mir17, mir31, mir138 and mir222: their content was significantly lower during osteogenic differentiation. Using bioinformatics approaches we identified predictable genestarget for each miRs, analyzed signaling networks and biological process enriched by these genes. Bioinformatic assay shows that miRNAs specifically involved in hMSCs transition into osteogenic differentiation via microenvironment formation (i.e. let7a, mir17, mir21, mir29b and mir101), TGFβ/BMP–SMAD dependent pathway (i.e. let7a, mir17, mir21, mir26a mir101) and MAPK signaling pathway (i.e. let7a, mir21, mir26a, mir29b, mir143 and mir17). Yapdependent expression of osteogenic transcriptional factors modulated by let7a, mir31mir101, mir138 and mir222. We predicted that mir17, mir26a, mir29b, mir101, mir138 and mir222 are specifically involved in canonical Wnt signaling dependent osteogenesis as well as in osteoblast maturation together with let7a, mir29b and mir218 which modulate AMPK signaling. Additionally, identified mir101 is likely involved into osteoblast homeostasis via Hedgehog signaling. Presented here data expands knowledge in the field of hMSCs fate and osteogenesis orchestration by miRs, points to proosteogenic and antiosteogenic miRs and their potential molecular pathways.
Keywords: cells signaling, differentiation, miR, microRNA, osteogenesis, osteogenic lineage, hMSCs
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