BioMetals

, Volume 24, Issue 5, pp 847–856 | Cite as

Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway

  • Kei-ichi Nakajima
  • Yosuke Kanno
  • Masato Nakamura
  • Xiao-Dong Gao
  • Asami Kawamura
  • Fumiaki Itoh
  • Akira Ishisaki
Article

Abstract

Lactoferrin (LF) belongs to the transferrin family and is present in several physiological fluids, including milk and colostrum. LF has recently been identified as an anabolic factor for bone. Here we investigated whether bovine LF (bLF) induces synthesis of angiogenic factors by osteoblasts. If so, we examined the underlying mechanism. We found that bLF purified from milk increased the mRNA expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF2) in murine osteoblast-like MC3T3-E1 cells and primary murine osteoblasts in a time- and dose-dependent manner. Furthermore, bLF increased VEGF and FGF2 protein levels in MC3T3-E1 cells. In addition, treatment of MC3T3-E1 cells with bLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase. The bLF-mediated increases in VEGF and FGF2 mRNA and protein were inhibited by U0126, a specific inhibitor of the upstream kinase that activates p44/p42 MAP kinase (MEK). Taken together, our results strongly suggest that bLF induces VEGF and FGF2 synthesis in a p44/p42 MAP kinase-dependent manner in MC3T3-E1 cells.

Keywords

FGF2 Lactoferrin Osteoblasts p44/p42 MAP kinase VEGF 

Abbreviations

LF

Lactoferrin

bLF

Bovine LF

VEGF

Vascular endothelial growth factor

FGF

Fibroblast growth factor

MAP

Mitogen-activated protein

FCS

Fetal calf serum

hLF

Human LF

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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • Kei-ichi Nakajima
    • 1
  • Yosuke Kanno
    • 2
  • Masato Nakamura
    • 1
  • Xiao-Dong Gao
    • 3
  • Asami Kawamura
    • 1
  • Fumiaki Itoh
    • 1
  • Akira Ishisaki
    • 4
  1. 1.National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research OrganizationSapporoJapan
  2. 2.Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical ScienceDoshisha Women’s College of Liberal ArtsKyotoJapan
  3. 3.Frontier Research Center for Post-Genomic Science and TechnologyHokkaido UniversitySapporoJapan
  4. 4.Department of BiochemistryIwate Medical University School of DentistryMoriokaJapan

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