Involvement of bone morphogenetic protein-related pathways in the effect of aucubin on the promotion of osteoblast differentiation in MG63 cells

Chem Biol Interact. 2018 Mar 1:283:51-58. doi: 10.1016/j.cbi.2018.02.005. Epub 2018 Feb 3.

Abstract

Aucubin, an iridoid glycoside found in several plants, such as Eucommia ulmoide and Rehmannia, has various pharmacological effects. Bone formation is a complex process in which osteoblast differentiation plays an important role. This study aimed to investigate the promotion effects of aucubin on osteoblast differentiation in MG63 cells, a human osteoblast-like cell line. Aucubin not only improved osteoblast differentiation, as shown by enhanced ALP (alkaline phosphatase) concentration and mineralization in cells, but increased the expression of various cytokines, including collagen I, osteocalcin, osteopontin, integrin β1, and Osterix. Aucubin strongly enhanced the levels of BMP2 (bone morphogenetic proteins-2) in MG63 cells, which play a central role during osteoblast differentiation. Further data show that aucubin exposure after 1 day, 7 days, and 14 days enhanced the expression of Smad1, 5, and 8, and the phosphoresced levels of MAPKs (mitogen-activated protein kinases) family Erk (extracellular signal-regulated kinases), JNK (c-Jun-NH2-terminal kinases), P38, and Akt (serine/threonine protein kinase)/mTOR (mammalian target of rapamycin)/p70s6k in MG63 cells. This study shows the improved effects of aucubin on osteoblast differentiation in MG63 cells, related to the signaling of BMP2-mediated Smads (drosophila mothers against decapentaplegic proteins), MAPKs, and Akt/mTOR/p70S6K. This study indicates the potential of aucubin for osteoporosis treatment.

Keywords: Aucubin; Bone morphogenetic protein 2 (BMP2); Differentiation; Osteoblast.

MeSH terms

  • Bone Morphogenetic Protein 2 / metabolism*
  • Cell Differentiation / drug effects*
  • Cell Line
  • Cell Proliferation / drug effects
  • Collagen Type I / metabolism
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Iridoid Glucosides / chemistry
  • Iridoid Glucosides / pharmacology*
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • MAP Kinase Signaling System / drug effects
  • Osteoblasts / cytology
  • Osteoblasts / drug effects
  • Osteoblasts / metabolism
  • Osteocalcin / metabolism
  • Osteopontin / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Smad1 Protein / metabolism
  • Smad5 Protein / metabolism
  • Smad8 Protein / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • BMP2 protein, human
  • Bone Morphogenetic Protein 2
  • Collagen Type I
  • Iridoid Glucosides
  • Smad1 Protein
  • Smad5 Protein
  • Smad8 Protein
  • Osteocalcin
  • Osteopontin
  • aucubin
  • Proto-Oncogene Proteins c-akt
  • Extracellular Signal-Regulated MAP Kinases
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases