Background:
Recent studies revealed that the hypoglycemic hormone, glucagon-like peptide-1 (GLP-1), acted as an important
modulator in osteogenesis of bone marrow derived mesenchymal stem cells (BMSCs).
Objectives:
The aim of this study was to identify the specific microRNA (miRNA) using bioinformatics analysis and validate the presence of
differentially expressed microRNAs with their target genes after GLP-1 receptor agonist (GLP-1RA) administration involved in ostogenesis
of BMSCs.
Methods:
MiRNAs were extracted from BMSCs after 5 days’ treatment and sent for high-throughput sequencing for differentially expressed
(DE) miRNAs analyses. Then the expression of the DE miRNAs verified by the real-time RT-PCR analyses. Target genes were predicted,
and highly enriched GOs and KEGG pathway analysis were conducted using bioinformatics analysis. For the functional study, two of the
target genes, SRY (sex determining region Y)-box 5 (SOX5) and G protein-coupled receptor 84 (GPR84), were identified.
Results:
A total of 5 miRNAs (miRNA-509-5p, miRNA-547-3p, miRNA-201-3p, miRNA-201-5p, and miRNA-novel-272-mature) were
identified differentially expressed among groups. The expression of miRNA-novel-272-mature were decreased during the osteogenic
differentiation of BMSCs, and GLP-1RA further decreased its expression. MiRNA-novel-272-mature might interact with its target mRNAs to
enhance osteogenesis. The lower expression of miRNA-novel-272-mature led to an increase in SOX5 and a decrease in GPR84 mRNA
expression, respectively.
Conclusions:
Taken together, these results provide further insights to the pharmacological properties of GLP-1RA
and expand our knowledge on the role of miRNAs-mRNAs regulation network in BMSCs’ differentiation.
G protein regulation of phospholipase C activity in a membrane-solubilized system occurs through a Mg2(+)- and time-dependent mechanism.
