+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

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

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

Biometals 24(5): 847-856

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.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 051852907

Download citation: RISBibTeXText

PMID: 21404021

DOI: 10.1007/s10534-011-9439-0

Related references

Rho-kinase inhibitors decrease TGF-beta-stimulated VEGF synthesis through stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts. Biochemical Pharmacology 77(2): 196-203, 2009

TSP-1, VEGF and FGF2 are key angiogenic mediators in the prostate. Journal of Urology 165(5 Suppl.): 51, 2001

p38 MAP kinase regulates BMP-4-stimulated VEGF synthesis via p70 S6 kinase in osteoblasts. American Journal of Physiology. Endocrinology and Metabolism 284(6): E1202-9, 2003

Angiogenic factors (VEGF, FGF and IGF) in the bovine corpus luteum. Journal of Reproduction and Development 48(3): 233-242, 2002

Cholestatic liver injury induces overexpression of angiogenic factors VEGF and bFGF. Hepatology 26(4 Part 2): 400A, 1997

FGF2 Modulation of Wnt Pathway in Osteoblasts. 2011

Resveratrol inhibits BMP-4-stimulated VEGF synthesis in osteoblasts: suppression of S6 kinase. International Journal of Molecular Medicine 33(4): 1013-1018, 2014

Involvement of AMP-activated protein kinase in TGF-β-stimulated VEGF synthesis in osteoblasts. International Journal of Molecular Medicine 29(4): 550-556, 2012

Lactoferrin secretion into mouse milk. Development of secretory activity, the localization of lactoferrin in the secretory pathway, and interactions of lactoferrin with milk iron. Advances in Experimental Medicine and Biology 443: 141-153, 1998

Glimepiride induces proliferation and differentiation of rat osteoblasts via the PI3-kinase/Akt pathway. Metabolism: Clinical and Experimental 59(3): 359-366, 2010

AMP-activated protein kinase positively regulates FGF-2-stimulated VEGF synthesis in osteoblasts. Biochemical and Biophysical Research Communications 400(1): 123-127, 2010

Rho-kinase limits BMP-4-stimulated osteocalcin synthesis in osteoblasts: regulation of the p38 MAP kinase pathway. Life Sciences 96(1-2): 18-25, 2014

Platelet factor 4 inhibits FGF2-induced endothelial cell proliferation via the extracellular signal-regulated kinase pathway but not by the phosphatidylinositol 3-kinase pathway. Blood 100(9): 3087-3094, 2002

Platelet-derived growth factor-BB amplifies PGF2alpha-stimulated VEGF synthesis in osteoblasts: function of phosphatidylinositol 3-kinase. Prostaglandins, Leukotrienes, and Essential Fatty Acids 77(3-4): 187-193, 2007