microRNA‐491‐5p regulates osteogenic differentiation of bone marrow stem cells in type 2 diabetes

Abstract

Objectives Osseointegration of oral implants has a low success rate in patients with type 2 diabetes. This is because of the inhibition of osteogenic differentiation in the jawbone marrow mesenchymal stem cells, in which the expression of microRNA(miR)‐491‐5p is significantly downregulated, as ascertained through gene chip screening. However, the underlying mechanisms are unclear. Here, we aimed to clarify the mechanisms involved in the influence of miR‐491‐5p on osteogenic differentiation. Subjects and methods: Jawbone marrow mesenchymal stem cells were isolated from jawbones of patients with type 2 diabetes and subjected to bioinformatics and functional analyses. Osteogenesis experiments were conducted using the isolated cells and an in vivo model. Results Knockdown and overexpression experiments revealed the positive effects of miR‐491‐5p expression on osteogenic differentiation in vivo and in vitro. Additionally, a dual‐luciferase assay revealed that miR‐491‐5p targeted the SMAD/RUNX2 pathway by inhibiting the expression of epidermal growth factor receptor. Conclusions miR‐491‐5p is vital in osteogenic differentiation of jawbone mesenchymal stem cells; its downregulation in type 2 diabetes could be a major cause of decreased osteogenic differentiation. Regulation of miR‐491‐5p expression could improve osteogenic differentiation of jawbone mesenchymal stem cells in patients with type 2 diabetes.

Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance

“…During aging, BMSCs are inclined to differentiate into adipocytes rather than osteoblasts, resulting in low bone mass and marrow fat accumulation (11). BMSCs differentiation is also altered in DM condition (12,13). BMSCs isolated from T1DM animal shows impaired ability of osteogenesis (12).…”

“…BMSCs isolated from T1DM animal shows impaired ability of osteogenesis (12). Dysregulated microRNA-491-5p expression in BMSCs isolated from T2DM patients contributes to the reduced ability of osteogenic differentiation (13). High glucose condition regulates MSCs osteogenic differentiation and adipogenic differentiation (14,15).…”