Select polyphenolic fractions from dried plum enhance osteoblast activity through BMP-2 signaling

J Nutr Biochem. 2018 May;55:59-67. doi: 10.1016/j.jnutbio.2017.09.014. Epub 2017 Sep 29.

Abstract

Dried plum supplementation has been shown to enhance bone formation while suppressing bone resorption. Evidence from previous studies has demonstrated that these responses can be attributed in part to the fruit's polyphenolic compounds. The purpose of this study was to identify the most bioactive polyphenolic fractions of dried plum with a focus on their osteogenic activity and to investigate their mechanisms of action under normal and inflammatory conditions. Utilizing chromatographic techniques, six fractions of polyphenolic compounds were prepared from a crude extract of dried plum. Initial screening assays revealed that two fractions (DP-FrA and DP-FrB) had the greatest osteogenic potential. Subsequent experiments using primary bone-marrow-derived osteoblast cultures demonstrated these two fractions enhanced extracellular alkaline phosphatase (ALP), an indicator of osteoblast activity, and mineralized nodule formation under normal conditions. Both fractions enhanced bone morphogenetic protein (BMP) signaling, as indicated by increased Bmp2 and Runx2 gene expression and protein levels of phosphorylated Smad1/5. DP-FrB was most effective at up-regulating Tak1 and Smad1, as well as protein levels of phospho-p38. Under inflammatory conditions, TNF-α suppressed ALP and tended to decrease nodule formation (P=.0674). This response coincided with suppressed gene expression of Bmp2 and the up-regulation of Smad6, an inhibitor of BMP signaling. DP-FrA and DP-FrB partially normalized these responses. Our results show that certain fractions of polyphenolic compounds in dried plum up-regulate osteoblast activity by enhancing BMP signaling, and when this pathway is inhibited by TNF-α, the osteogenic response is attenuated.

Keywords: Bone morphogenetic proteins; Functional foods; Osteoblast; Osteoporosis; Polyphenol.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Marrow
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Protein 2 / metabolism*
  • Calcification, Physiologic / drug effects
  • Cells, Cultured
  • Female
  • Gene Expression Regulation / drug effects
  • MAP Kinase Signaling System / drug effects
  • Mice, Inbred C57BL
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism
  • Polyphenols / pharmacology*
  • Prunus domestica / chemistry*
  • Signal Transduction / drug effects
  • Smad6 Protein / genetics
  • Smad6 Protein / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Polyphenols
  • Smad6 Protein
  • Smad6 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Alkaline Phosphatase