MicroRNA-483-5p inhibits osteogenic differentiation of human bone marrow mesenchymal stem cells by targeting the RPL31-mediated RAS/MEK/ERK signaling pathway

Abstract

miR-483-5p has been shown to play a key regulatory role in mediating a variety of biological activities. However, there are only a few studies on how miR-483-5p regulates osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs), hence there is a need to explore the role and mechanism of miR-483-5p in regulating the osteogenic differentiation of hBMSCs. To that end, we used bioinformatics and cell experiments to confirm our hypothesis, a miRNA microarray dataset (GSE74209) and a mRNA dataset (GSE56816) were obtained from the GEO database, and the differentially expressed miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were screened. In total, We found that the up-regulated candidate target genes were significantly enriched in the MAPK signaling pathway. Using the MCODE plug-in from Cytoscape, we identified RPL31 as the seed gene in the third major module. And we successfully established a possible miRNA-hub gene regulatory network. More importantly, we confirmed that the expression of miR-483-5p was down-regulated while the expression of RPL31 was up-regulated during osteogenic induction. Overexpression of miR-483-5p significantly inhibited osteogenic differentiation. In addition, western blot was used to measure protein levels of RPL31 and phosphorylated MEK/ERK family members. We demonstrated that miR-483-5p inhibits the RAS/MEK/ERK signaling pathway by targeting RPL31 and inhibiting its expression, thereby playing an inhibitory role in osteogenic differentiation. In light of our findings, RPL31 can be used as a novel therapeutic target for bone defects and osteoporosis, we reveal a newly discovered mechanism of osteogenic differentiation and provide a new strategy for treating osteoporosis and related diseases.