Harmine promotes molar root development via SMAD1/5/8 phosphorylation

Biochem Biophys Res Commun. 2018 Mar 11;497(3):924-929. doi: 10.1016/j.bbrc.2017.12.062. Epub 2017 Dec 15.

Abstract

Tooth and bone are major tissues involved in physiological calcification in the body, and they use similar molecular pathways for development, homeostasis, and regeneration. Harmine (HMN) is a natural small compound that stimulates osteoblast differentiation in vitro and in vivo. Here we examined the biological effect of HMN on the postnatal development of molar tooth roots and periodontal tissues. HMN supported the formation of tooth roots and periodontal tissues in developing tooth germs. In tooth germ organ culture, HMN promoted the elongation of Hertwig's epithelial root sheath (HERS) and stimulated cell proliferation in HERS and dental follicle-derived tissues, including dental papillae and dental follicles. HMN stimulated cell proliferation and cell movement of HERS-derived cells without mesenchymal cells in vitro and directly induced the phosphorylation of SMAD1/5/8 protein in HERS-derived cells. Our results indicated that HMN was the first natural small compound to stimulate postnatal development of tooth germs.

Keywords: Cell movement; Cell proliferation; Hertwig's epithelial root sheath; Natural small compound; Postnatal development; Tooth root.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Harmine / pharmacology*
  • Mice, Inbred C57BL
  • Molar / drug effects*
  • Molar / growth & development
  • Molar / metabolism
  • Phosphorylation / drug effects*
  • Smad1 Protein / analysis
  • Smad1 Protein / metabolism*
  • Smad5 Protein / analysis
  • Smad5 Protein / metabolism*
  • Smad8 Protein / analysis
  • Smad8 Protein / metabolism*
  • Tooth Root / drug effects*
  • Tooth Root / growth & development
  • Tooth Root / metabolism

Substances

  • Smad1 Protein
  • Smad1 protein, mouse
  • Smad5 Protein
  • Smad5 protein, mouse
  • Smad8 Protein
  • Smad9 protein, mouse
  • Harmine