title: Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway.
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.
authors.affiliation: National Agricultural Research Center for Hokkaido Region, National Agriculture and Food Research Organization, 1 Hitsujigaoka, Toyohira-Ku, Sapporo 062-8555, Japan. k1nakaji@affrc.go.jp
authors.forename: Kei-Ichi
authors.initials: K
authors.lastname: Nakajima
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Kanno
authors.forename: Masato
authors.initials: M
authors.lastname: Nakamura
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Gao
authors.forename: Asami
authors.initials: A
authors.lastname: Kawamura
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Itoh
authors.forename: Akira
authors.initials: A
authors.lastname: Ishisaki
mesh_terms: D000818:Animals; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D007781:Lactoferrin / Q000302:isolation & purification / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D008892:Milk / Q000737:chemistry*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D002070:Butadienes; D009570:Nitriles; D012333:RNA, Messenger; C113580:U 0126; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D007781:Lactoferrin