Food for Bone: Evidence for a Role for Delta-Tocotrienol in the Physiological Control of Osteoblast Migration

Int J Mol Sci. 2020 Jun 30;21(13):4661. doi: 10.3390/ijms21134661.

Abstract

Bone remodeling and repair require osteogenic cells to reach the sites that need to be rebuilt, indicating that stimulation of osteoblast migration could be a promising osteoanabolic strategy. We showed that purified δ-tocotrienol (δ-TT, 10 μg/mL), isolated from commercial palm oil (Elaeis guineensis) fraction, stimulates the migration of both MC3T3-E1 osteoblast-like cells and primary human bone marrow mesenchymal stem cells (BMSC) as detected by wound healing assay or Boyden chamber assay respectively. The ability of δ-TT to promote MC3T3-E1 cells migration is dependent on Akt phosphorylation detected by Western blotting and involves Wnt/β-catenin signalling pathway activation. In fact, δ-TT increased β-catenin transcriptional activity, measured using a Nano luciferase assay and pretreatment with procaine (2 µM), an inhibitor of the Wnt/β-catenin signalling pathway, reducing the wound healing activity of δ-TT on MC3T3-E1 cells. Moreover, δ-TT treatment increased the expression of β-catenin specific target genes, such as Osteocalcin and Bone Morphogenetic Protein-2, involved in osteoblast differentiation and migration, and increased alkaline phosphatase and collagen content, osteoblast differentiation markers. The ability of δ-TT to enhance the recruitment of BMSC, and to promote MC3T3-E1 differentiation and migratory behavior, indicates that δ-TT could be considered a promising natural anabolic compound.

Keywords: H3 and H4 acetylation level; MC3T3-E1 cells; Wnt/β-catenin pathway; delta-tocotrienol; osteoblast migration.

MeSH terms

  • Animals
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Movement / drug effects*
  • Drug Evaluation, Preclinical
  • Histone Acetyltransferases / metabolism
  • Mice
  • Osteoblasts / drug effects*
  • Transcriptional Activation / drug effects
  • Vitamin E / analogs & derivatives*
  • Vitamin E / pharmacology
  • beta Catenin / metabolism

Substances

  • beta Catenin
  • Vitamin E
  • tocotrienol, delta
  • Histone Acetyltransferases