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

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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.

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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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Authors and Affiliations

  1. National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, Sapporo, 062-8555, Japan

    Kei-ichi Nakajima, Masato Nakamura, Asami Kawamura & Fumiaki Itoh

  2. Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women’s College of Liberal Arts, 97-1 Kodo, Kyo-tanabe, Kyoto, Japan

    Yosuke Kanno

  3. Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Sapporo, Japan

    Xiao-Dong Gao

  4. Department of Biochemistry, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan

    Akira Ishisaki

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  1. Kei-ichi Nakajima
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  2. Yosuke Kanno
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  3. Masato Nakamura
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  5. Asami Kawamura
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Correspondence to Kei-ichi Nakajima.

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Nakajima, Ki., Kanno, Y., Nakamura, M. et al. Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway. Biometals 24, 847–856 (2011). https://doi.org/10.1007/s10534-011-9439-0

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