Inhibition effects of a natural inhibitor on RANKL downstream cellular signalling cascades cross-talking

J Cell Mol Med. 2018 Sep;22(9):4236-4242. doi: 10.1111/jcmm.13703. Epub 2018 Jun 17.

Abstract

Myricitrin is a natural occurring flavonoid glycoside that possesses effects on inhibiting nitric oxide (NO) transmission and preventing inflammatory reaction. Although previous study showed the myricitrin possesses antibone loss effects via reducing the expression of IL-6 and partially suppressing reactive oxygen species (ROS) production. However, the effects of myricitrin on nuclear factor-kappaB ligand (RANKL)-stimulated osteoclastogenesis have not yet been further investigated. The current study was aimed to demonstrating the inhibitory effects of myricitrin on RANKL-stimulated osteoclastogenesis and relevant mechanisms. We found myricitrin significantly suppressed osteoclastogenesis suggesting that it may acts on RANKL/RANK induced downstream signal cross cascading in osteoclast precursors. In that, our Western blotting results showed myricitrin significantly attenuated RNAKL/MAPKs (phosphorylation of p38, ERK, JNK) and AKT signal cascading. Complementing previous study, our results suggesting as a natural inhibitor, myricitrin possesses the potential therapeutic effects on inflammatory osteolysis.

Keywords: BMMs; NFATc1; myricitrin; osteoclastogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Bone Density Conservation Agents / pharmacology*
  • Cell Differentiation
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Flavonoids / pharmacology*
  • Gene Expression Regulation
  • MAP Kinase Kinase 4 / genetics
  • MAP Kinase Kinase 4 / metabolism
  • Macrophages / cytology
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred ICR
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Osteoclasts / cytology
  • Osteoclasts / drug effects*
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-akt / metabolism
  • RANK Ligand / antagonists & inhibitors
  • RANK Ligand / genetics*
  • RANK Ligand / metabolism
  • Receptor Activator of Nuclear Factor-kappa B / genetics*
  • Receptor Activator of Nuclear Factor-kappa B / metabolism
  • Signal Transduction
  • p38 Mitogen-Activated Protein Kinases / genetics
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Bone Density Conservation Agents
  • Flavonoids
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • myricitrin
  • Proto-Oncogene Proteins c-akt
  • Mapk1 protein, mouse
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4