Viburnum opulus L. Juice Phenolic Compounds Influence Osteogenic Differentiation in Human Osteosarcoma Saos-2 Cells

Int J Mol Sci. 2020 Jul 11;21(14):4909. doi: 10.3390/ijms21144909.

Abstract

Bone mass loss occurs with a decrease in osteoblast proliferation and differentiation, or the enhancement of bone resorption, which further leads to the impairment of bone mineral density and increase in bone fracture. Recent studies suggest that some phenolic compounds found in food play positive role in bone metabolism. High content of phenolic compounds with potential beneficial effects on bone metabolism have been identified in the Viburnum opulus fruit. The aim of the study was to determine the influence of V. opulus fresh juice (FJ) and juice purified by solid phase extraction (PJ) on osteogenesis processes with osteosarcoma Saos-2 cell lines. V. opulus purified juice revealed stronger potential as an inducer of Saos-2 osteogenic differentiation. Saos-2 cells matrix mineralization was evaluated with alkaline phosphatase (ALP) activity measurement and alizarin red S staining. Gene expression analysis showed the elevation of the mRNA levels of Runt-related transcription factor 2 (RUNX2), ALP, collagen type 1 and osteonectin, whereas the nuclear factor-κB ligand and osteoprotegerin ratio (RANKL/OPG) decreased. Furthermore, V. opulus was able to diminish the secretion of pro-inflammatory cytokines Il6 and TNFα, however had no effect on vascular endothelial growth factor (VEGF). It decreased intracellular oxidative stress and induced DNA repair, but had no effect on the growth inhibition of lactic acid beneficial microorganisms.

Keywords: Saos-2; Viburnum opulus; phenolic compounds.

MeSH terms

  • Bacteria / drug effects
  • Bone Density Conservation Agents / pharmacology*
  • Bone Neoplasms / pathology*
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • DNA Repair / drug effects
  • Drug Evaluation, Preclinical
  • Fruit and Vegetable Juices / analysis*
  • Gastrointestinal Microbiome / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Interleukin-6 / metabolism
  • Mitochondria / drug effects
  • Mitochondria / enzymology
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Osteosarcoma / pathology*
  • Oxidative Stress / drug effects
  • Phenols / pharmacology*
  • Plant Extracts / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Tumor Necrosis Factor-alpha / metabolism
  • Vascular Endothelial Growth Factor A / metabolism
  • Viburnum / chemistry*

Substances

  • Bone Density Conservation Agents
  • IL6 protein, human
  • Interleukin-6
  • Neoplasm Proteins
  • Phenols
  • Plant Extracts
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A