Osteoprotegerin in human milk: a potential role in the regulation of bone metabolism and immune development.
Osteoprotegerin (OPG) is a member of the tumor necrosis factor superfamily. It is a soluble "decoy" receptor for tumor necrosis factor-related apoptosis-inducing ligand and ligand of the receptor activator of NF-kappaB. As such, OPG inhibits osteoclast activity and regulates the immune system. Human milk is a complex biologic fluid that supplies nutritional and protective factors to the breast-fed infant. In the present study, human milk samples at various times postpartum were assessed for the presence of OPG. Using biochemical as well as immunologic and biologic techniques we showed that human milk contains OPG at a level that is 1000-fold higher than that found in normal human serum. We observed that human breast milk cells and the human mammary epithelial cell line MCF-7 express OPG, indicating that both cell types are possible sources of milk OPG in vivo. In vitro studies demonstrated that milk OPG is biologically active and suggested that it may contribute to the antiresorptive activity of milk on bone, as well as tumor necrosis factor-related apoptosis-inducing ligand-induced inhibition of T cell proliferation. OPG-like activity was also observed in bovine colostrum and milk. Furthermore, we were able to detect human OPG in the sera of rats gavaged with human milk. We discuss the relevance of our findings for the breast-fed infant and for the prevention of immune and bone disorders.
Vidal
Karine
K
Nestec Limited, Nestlé Research Center, Food Immunology, Vers-chez-les-Blanc, P.O. Box 44, CH-1000 Lausanne 26, Switzerland. karine.vidal@rdls.nestle.com
van den Broek
Peter
P
Lorget
Florence
F
Donnet-Hughes
Anne
A
D051722:ADAM Proteins; D000072198:ADAM17 Protein; D000818:Animals; D001483:Base Sequence; D001862:Bone Resorption / Q000517:prevention & control; D001842:Bone and Bones / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics; D002417:Cattle; D002455:Cell Division; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000235:genetics; D008666:Metalloendopeptidases / Q000235:genetics; D008895:Milk, Human / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D053244:Osteoprotegerin; D053245:RANK Ligand; D051381:Rats; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor
D002352:Carrier Proteins; D018076:DNA, Complementary; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D053244:Osteoprotegerin; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; C506032:Tnfrsf11b protein, rat; D051722:ADAM Proteins; D008666:Metalloendopeptidases; D000072198:ADAM17 Protein