Mogroside V enhances bone marrow mesenchymal stem cells osteogenesis under hyperglycemic conditions through upregulating miR-10b-5p and PI3K/Akt signaling

Abstract Background Mogroside V (MV) is a triterpene glucoside that reportedly exhibits an array of antitumor, anti-inflammatory, hypolipidemic, and hypoglycemic properties. In prior studies, our group determined that MV was able to readily enhance osteogenic bone marrow mesenchymal stem cells (BMSCs) differentiation under high-glucose conditions through mechanisms potentially associated with miR-10b-5p and PI3K/Akt signaling activity. The precise molecular basis for these effects, however, remains to be fully elucidated. Objective This study aims to explore the potential mechanisms by which MV regulates the osteogenic differentiation of BMSCs under hyperglycemic conditions. Methods Femoral and tibial BMSCs were isolated from control and diabetic C57BL/6J mice. qRT-PCR was used to quantify miR-10b-5p levels. Putative miR-10b-5p target genes were predicted through bioinformatics assays and validated in a luciferase reporter assay system. miR-10b-5p expression was inhibited with an antagomiR-10b-5p construct, while PI3K/Akt pathway signaling was inhibited with LY294002. Western blotting was used to detect PI3K/Akt pathway and target gene protein levels, while Alizarin red staining was used to detect calcium nodule deposition by BMSCs. Results miR-10b-5p upregulation was noted in BMSCs exposed to hyperglycemic conditions. HOXD10 was identified as a cell differentiation-related miR-10b-5p target gene in bioinformatics analyses, and the targeting relationship between the two was confirmed in a luciferase reporter assay. MV treatment elicited significantly higher levels of miR-10b-5p expression, PI3K phosphorylation, and calcium deposition, while antagomiR-10b-5p or LY294002 treatment reversed these changes, and the opposite trends were observed with respect to HOXD10 protein levels. Conclusion MV favors BMSCs osteogenic differentiation under high-glucose conditions through the upregulation of miR-10b-5p and the activation of PI3K/Akt signaling.