Simvastatin exerts antiproliferative and differentiating effects on MG63 osteoblast-like cells: Morphological and immunocytochemical study

J Periodontal Res. 2018 Feb;53(1):91-97. doi: 10.1111/jre.12491. Epub 2017 Sep 4.

Abstract

Background and objective: Current evidence suggests that statins exert an anabolic effect on bone and may therefore impact on osteogenic differentiation and proliferation. These effects can be useful for their use in guided bone regeneration. The objective of this study was to determine the in vitro effects of simvastatin on the differentiation and proliferation of MG63 human osteoblast tumor cells.

Material and methods: MG63 human osteosarcoma cells were cultured in the presence of simvastatin or solvent alone for 72 hours, and their proliferation was assessed by MTT assay. Cells from the culture were prepared for light, transmission and scanning electron microscopy studies. immunocytochemical was used to analyze the differentiation and proliferation markers Musashi-1, Ki-67, CD56 and CD44.

Results: Cultured MG63 control cells showed spheroid morphology with numerous secretion vesicles accumulated on the surface, observing no cytoplasmic projections with intercellular connections. However, cells cultured with simvastatin had a polygonal and spindle-shaped morphology, with cytoplasmic projections that interconnected cells. There were numerous microvilli-like filamentous projections on the surface with no defined pattern. At 72 hours of culture, CD56, Ki-67 and Musashi-1 expression was significantly reduced (P < .001) in simvastatin-treated cells. CD44 expression was intense in both groups and was not affected by simvastatin treatment.

Conclusion: MG63 cells cultured with simvastatin for 72 hours undergo morphological and surface changes. Simvastatin treatment exerts antiproliferative and differentiating effects on these cells as well as promoting recovery of cellular homeostasis.

Keywords: Simvastatin; cell differentiation; cell proliferation; electron microscopy; immunohistochemistry; osteoblasts.

MeSH terms

  • CD56 Antigen / metabolism
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects*
  • Cells, Cultured
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Ki-67 Antigen / metabolism
  • Microscopy
  • Nerve Tissue Proteins / metabolism
  • Osteoblasts / drug effects*
  • Osteoblasts / ultrastructure
  • RNA-Binding Proteins / metabolism
  • Simvastatin / pharmacology*

Substances

  • CD56 Antigen
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ki-67 Antigen
  • MSI1 protein, human
  • NCAM1 protein, human
  • Nerve Tissue Proteins
  • RNA-Binding Proteins
  • Simvastatin