Menaquinone-7 regulates gene expression in osteoblastic MC3T3E1 cells

Int J Mol Med. 2007 Feb;19(2):279-84.

Abstract

Previous study has shown that the vitamin K2 analog menaquinone-7 (MK-7) induces expression of the osteoblast-specific genes osteocalcin, osteoprotegerin, receptor activator of NFkappaB, and its ligand. Since MK-7 may also regulate osteoblast cell function, we examined the expression of osteoblast genes regulated by MK-7 administration. Differences between gene expression in control and MK-7-administered MC3T3E1 cells were analyzed using the suppression subtractive hybridization method. After 24 h of MK-7 administration, genes upregulated by MK-7 included tenascin C and BMP2. Genes downregulated by MK-7 administration included biglycan and butyrophilin. Real-time PCR showed a marked increase in tenascin C. When the protein level was examined using Western blot analysis, tenascin C was higher in MK-7-administered cells than in control cells. These results indicated that MK-7 affected the cellular function of osteoblastic MC3T3E1 cells. Considering BMP2 mRNA expression was higher in MK-7-administered cells than in control cells, the effect of MK-7 administration on the signal transduction system was examined. Western blot analysis showed that cells administered MK-7 displayed a higher phosphorylated Smad1 level than control cells. Because MC3T3E1 cells have a nuclear binding receptor for MK-7, this result might indicate an indirect effect of MK-7 through BMP2 production.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Gene Expression Regulation / drug effects*
  • Mice
  • Nucleic Acid Hybridization
  • Osteoblasts / drug effects*
  • Osteoblasts / metabolism*
  • RNA, Messenger / genetics
  • Signal Transduction
  • Tenascin / genetics
  • Vitamin K 2 / analogs & derivatives*
  • Vitamin K 2 / pharmacology

Substances

  • RNA, Messenger
  • Tenascin
  • Vitamin K 2
  • vitamin MK 7