Abstract
BackgroundOur previous study showed that (+)-cholesten-3-one (CN) has the potential to induce the osteoblastic differentiation of mesenchymal stem cells (MSCs). However, the roles of CN in targeting miRNA-mRNA-lncRNA interactions to regulate osteoblast differentiation remain poorly understood.ResultsA total of 77 miRNAs (36 upregulated and 41 downregulated) and 295 lncRNAs (281 upregulated and 14 downregulated) were significantly differentially expressed during CN-induced MSC osteogenic differentiation. Bioinformatic analysis identified that several pathways may play vital roles in MSC osteogenic differentiation, such as the vitamin D receptor signalling, TNF signalling, PI3K-Akt signalling, calcium signalling, and mineral absorption pathways. Further bioinformatic analysis revealed 16 core genes, including 6 mRNAs (Vdr, Mgp, Fabp3, Fst, Cd38, and Col1a1), 5 miRNAs (miR-483, miR-298, miR-361, miR-92b and miR-155) and 5 lncRNAs (NR_046246.1, NR_046239.1, XR_086062.1, XR_145872.1 and XR_146737.1), that may play important roles in regulating the CN-induced osteogenic differentiation of MSCs. Verified by the luciferase reporter, AR-S, qRT-PCR and western blot assays, we identified one miRNA (miR-298) that may enhance the osteogenic differentiation potential of MSCs via the vitamin D receptor signalling pathway.ConclusionsThis study revealed the global expression profile of miRNAs and lncRNAs involved in the Chinese medicine active ingredient CN-induced osteoblast differentiation of MSCs for the first time and provided a foundation for future investigations of miRNA-mRNA-lncRNA interaction networks to completely illuminate the regulatory role of CN in MSC osteoblast differentiation.
Highlights
Our previous study showed that (+)-cholesten-3-one (CN) has the potential to induce the osteoblastic differentiation of mesenchymal stem cells (MSCs)
CN-induced MSC osteoblastic differentiation A total of 77 differentially expressed miRNAs were identified during CN-induced osteoblast differentiation compared to uninduced MSCs (P < 0.05); among them, 36 were upregulated and 41 were downregulated
A total of 443 possible mRNAs were predicted to targeted by differentially expressed miRNA and long-chain noncoding RNAs (lncRNAs) during CN-induced osteoblast differentiation compared to uninduced MSCs (P < 0.05); of these, 223 were predicted to be upregulated, and 220 were predicted to be downregulated (P < 0.05) (Additional file 2)
Summary
Our previous study showed that (+)-cholesten-3-one (CN) has the potential to induce the osteoblastic differentiation of mesenchymal stem cells (MSCs). The roles of CN in targeting miRNA-mRNA-lncRNA interactions to regulate osteoblast differentiation remain poorly understood. Increasing evidence [15,16,17] has shown that lncRNAs regulate gene expression by interacting with DNA, RNA or proteins, but identifying the functions of individual lncRNAs remains challenging [18,19,20]. Previous studies [21, 22] have reported that miRNA-mRNA-lncRNA interaction networks play important roles in biological processes. None of these interaction networks have been shown to regulate the CN-induced osteoblast differentiation of MSCs. further research is required to investigate the miRNA-mRNA-lncRNA interaction network in the CN-induced osteoblast differentiation of MSCs
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