Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity

Lactoferrin (LF) is a key modulator of inflammatory response. Since bone and immune systems are genetically and functionally linked, we were interested to know if LF could influence bone remodeling. Bovine LF (bLF) inhibited in vitro bone resorbing activity (IC50, 200 μg/ml) in a rabbit mixed bone c...

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Published in:Biochemical and biophysical research communications 2002-08, Vol.296 (2), p.261-266
Main Authors: Lorget, Florence, Clough, Jennifer, Oliveira, Manuel, Daury, Marc-Cedric, Sabokbar, Afsie, Offord, Elizabeth
Format: Article
Language:English
Subjects:
Animals
Bone Resorption
Bovine lactoferrin
Carrier Proteins - pharmacology
Cattle
CD14 selected cells
Cell Differentiation - physiology
Cells, Cultured
Differentiation
Glycoproteins - genetics
Glycoproteins - metabolism
Humans
Lactoferrin - pharmacology
Lipopolysaccharide Receptors - metabolism
Macrophage Colony-Stimulating Factor - metabolism
Membrane Glycoproteins - pharmacology
NF-kappa B - metabolism
Osteoclast
Osteoclasts - cytology
Osteoclasts - drug effects
Osteoclasts - physiology
Osteoprotegerin
Phenotype
Rabbits
RANK Ligand
Receptor Activator of Nuclear Factor-kappa B
Receptors, Calcitonin - genetics
Receptors, Calcitonin - metabolism
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - metabolism
Receptors, Tumor Necrosis Factor
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Summary:Lactoferrin (LF) is a key modulator of inflammatory response. Since bone and immune systems are genetically and functionally linked, we were interested to know if LF could influence bone remodeling. Bovine LF (bLF) inhibited in vitro bone resorbing activity (IC50, 200 μg/ml) in a rabbit mixed bone cell culture, consisting of authentic osteoclasts in an environment of osteoblast and stromal cells. Using human CD14 selected cells committed toward osteoclasts, bLF (10 μg/ml) stimulated cell proliferation, however, led to an inhibition of calcitonin receptor mRNA expression, a main marker of osteoclast phenotype, and decreased the global resorbing activity. No modulation of RANK mRNA expression was observed and mRNA for RANKL and OPG were not detected in this culture system, suggesting that bLF inhibits osteoclastogenesis and reduces bone resorption through a mechanism independent of OPG/RANKL/RANK. In conclusion, bLF appears to modulate bone remodeling. Its mechanism of action remains to be elucidated.
ISSN:0006-291X
1090-2104
DOI:10.1016/S0006-291X(02)00849-5