MicroRNA-21 affects mechanical force-induced midpalatal suture remodelling

Cell Prolif. 2020 Jan;53(1):e12697. doi: 10.1111/cpr.12697. Epub 2019 Nov 12.

Abstract

Objectives: miR-21 can promote osteoblast differentiation of periodontal ligament stem cells. However, the effect of miR-21 on bone remodelling in the midpalatal suture is unclear. This study aimed to elucidate the effects of miR-21 on the midpalatal suture bone remodelling by expanding the palatal sutures.

Materials and methods: miR-21 deficient (miR-21-/- ) and wild-type (WT) mice were used to establish animal models by expanding the palatal sutures. Micro-CT, haematoxylin-eosin (HE) staining, tartrate-resistant acid phosphatase (TRAP) staining, fluorescence labelling and immunohistochemistry were used to investigate the function of miR-21 in midpalatal suture bone remodelling. Besides, bone mesenchymal stem cells (BMSCs) derived from both miR-21-/- and WT mice were cultured. The MTT, CCK8, EdU analysis, transwell and wound healing test were used to assess the effects of miR-21 on the characteristics of cells.

Results: The expression of ALP was suppressed in miR-21-/- mice after expansion except 28 days. The expression of Ocn in WT mice was much higher than that of miR-21-/- mice. Besides, with mechanical force, miR-21 deficiency downregulated the expression of Opg, upregulated the expression of Rankl, and induced more osteoclasts as TRAP staining showed. After injecting agomir-21 to miR-21-/- mice, the expression of Alp, Ocn and Opg/Rankl were rescued. In vitro, the experiments suggested that miR-21 deficiency reduced proliferation and migration ability of BMSCs.

Conclusions: The results showed that miR-21 deficiency reduced the rate of bone formation and prolonged the process of bone formation. miR-21 regulated the bone resorption and osteoclastogenesis by affecting the cell abilities of proliferation and migration.

Keywords: bone remodelling; mineralized tissue; osteoblast; osteoclast.

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / metabolism*
  • Bone Remodeling*
  • Cell Differentiation
  • Cell Proliferation
  • Cranial Sutures / cytology
  • Cranial Sutures / metabolism*
  • Gene Expression Regulation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Knockout
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteoprotegerin / biosynthesis
  • Osteoprotegerin / genetics
  • Palate / cytology
  • Palate / metabolism*
  • RANK Ligand / biosynthesis
  • RANK Ligand / genetics
  • Stress, Mechanical*
  • Tartrate-Resistant Acid Phosphatase / biosynthesis
  • Tartrate-Resistant Acid Phosphatase / genetics

Substances

  • MIRN21 microRNA, mouse
  • MicroRNAs
  • Osteoprotegerin
  • RANK Ligand
  • Tnfrsf11b protein, mouse
  • Tnfsf11 protein, mouse
  • Acp5 protein, mouse
  • Tartrate-Resistant Acid Phosphatase