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

Oral Dis. 2023 Jan;29(1):308-321. doi: 10.1111/odi.14005. Epub 2021 Oct 7.

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.

Keywords: cell differentiation; diabetes; microRNA; oral implants; osseointegration; stem cell(s).

MeSH terms

  • Bone Marrow Cells
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Diabetes Mellitus, Type 2* / genetics
  • Humans
  • MicroRNAs* / metabolism
  • Osteogenesis / genetics

Substances

  • MicroRNAs
  • MIRN491 microRNA, human