Dioxinodehydroeckol Enhances the Differentiation of Osteoblasts by Regulating the Expression of Phospho-Smad1/5/8

Mar Drugs. 2016 Sep 14;14(9):168. doi: 10.3390/md14090168.

Abstract

Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 μM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP) signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction.

Keywords: BMP-2; Ecklonia cava; Smad; dioxinodehydroeckol; osteoblastogenesis.

MeSH terms

  • 3T3 Cells
  • Alkaline Phosphatase / metabolism
  • Animals
  • Bone Morphogenetic Protein 2 / biosynthesis
  • Bone Morphogenetic Protein 2 / genetics
  • Bone Morphogenetic Proteins / drug effects
  • Cell Differentiation / drug effects*
  • Cell Proliferation / drug effects
  • Collagen Type I / biosynthesis
  • Collagen Type I / genetics
  • Dioxins / pharmacology*
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Osteoblasts / drug effects*
  • Osteoporosis / prevention & control
  • Phaeophyceae / chemistry
  • RNA / biosynthesis
  • RNA / genetics
  • Signal Transduction / drug effects
  • Smad Proteins / biosynthesis*
  • Smad Proteins / genetics*

Substances

  • Bmp2 protein, mouse
  • Bone Morphogenetic Protein 2
  • Bone Morphogenetic Proteins
  • Collagen Type I
  • Dioxins
  • Smad Proteins
  • dioxinodehydroeckol
  • RNA
  • Alkaline Phosphatase