caa a22 4500 445321873 CHVBK 20180317142706.0 cr unu---uuuuu 170323e20111001xx s 000 0 eng 10.1007/s10534-011-9439-0 doi (NATIONALLICENCE)springer-10.1007/s10534-011-9439-0 Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway [Elektronische Daten] [Kei-ichi Nakajima, Yosuke Kanno, Masato Nakamura, Xiao-Dong Gao, Asami Kawamura, Fumiaki Itoh, Akira Ishisaki] 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. Springer Science+Business Media, LLC., 2011 FGF2 nationallicence Lactoferrin nationallicence Osteoblasts nationallicence p44/p42 MAP kinase nationallicence VEGF nationallicence LF : Lactoferrin nationallicence bLF : Bovine LF nationallicence VEGF : Vascular endothelial growth factor nationallicence FGF : Fibroblast growth factor nationallicence MAP : Mitogen-activated protein nationallicence FCS : Fetal calf serum nationallicence hLF : Human LF nationallicence Nakajima Kei-ichi National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut Kanno Yosuke Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, 97-1 Kodo, Kyo-tanabe, Kyoto, Japan aut Nakamura Masato National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut Gao Xiao-Dong Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Sapporo, Japan aut Kawamura Asami National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut Itoh Fumiaki National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut Ishisaki Akira Department of Biochemistry, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan aut BioMetals Springer Netherlands 24/5(2011-10-01), 847-856 0966-0844 24:5<847 2011 24 10534 https://doi.org/10.1007/s10534-011-9439-0 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10534-011-9439-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nakajima Kei-ichi National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut NATIONALLICENCE 700 1- Kanno Yosuke Department of Clinical Pathological Biochemistry, Faculty of Pharmaceutical Science, Doshisha Women's College of Liberal Arts, 97-1 Kodo, Kyo-tanabe, Kyoto, Japan aut NATIONALLICENCE 700 1- Nakamura Masato National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut NATIONALLICENCE 700 1- Gao Xiao-Dong Frontier Research Center for Post-Genomic Science and Technology, Hokkaido University, Sapporo, Japan aut NATIONALLICENCE 700 1- Kawamura Asami National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut NATIONALLICENCE 700 1- Itoh Fumiaki National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, 062-8555, Sapporo, Japan aut NATIONALLICENCE 700 1- Ishisaki Akira Department of Biochemistry, Iwate Medical University School of Dentistry, Morioka, Iwate, Japan aut NATIONALLICENCE 773 0- BioMetals Springer Netherlands 24/5(2011-10-01), 847-856 0966-0844 24:5<847 2011 24 10534 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer