Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells

ABSTRACT: Insufficient absorption of iron and the consequent development of iron deficiency have serious health consequences. Hence, identification and development of iron delivery systems that can increase the bioavailability and uptake of dietary iron are important. Osteopontin (OPN) is an acidic...

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Main Authors: Emilie H. Buhl, Brian Christensen, Freja H. Pedersen, Esben S. S⊘rensen
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Journal of Dairy Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S0022030224012359
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author Emilie H. Buhl
Brian Christensen
Freja H. Pedersen
Esben S. S⊘rensen
author_facet Emilie H. Buhl
Brian Christensen
Freja H. Pedersen
Esben S. S⊘rensen
author_sort Emilie H. Buhl
collection DOAJ
description ABSTRACT: Insufficient absorption of iron and the consequent development of iron deficiency have serious health consequences. Hence, identification and development of iron delivery systems that can increase the bioavailability and uptake of dietary iron are important. Osteopontin (OPN) is an acidic and highly phosphorylated integrin-binding protein found in milk where it exists as a full-length protein and as N-terminally derived fragments. Milk OPN can be taken up by enterocytes and transported across the intestinal barrier into the circulation. Milk OPN has previously been shown to bind calcium and magnesium. This study investigates milk OPN as a carrier of iron and its potential to increase iron absorption in intestinal cells. Full-length OPN and N-terminal fragments of OPN were shown to bind ∼30 and ∼10 mol of iron, respectively, and the phosphorylated residues were crucial for iron binding. Osteopontin retained iron bound after simulated gastrointestinal digestion. Immunodetection of digested OPN and OPN-Fe complexes showed that the OPN-Fe complexes were more resistant to pepsin digestion than OPN without bound iron. The cellular uptake of iron was investigated by measuring intracellular ferritin formation and mRNA expression of divalent metal transporter 1 in Caco-2 cells. Osteopontin increased the uptake of iron even in the presence of phytic acid, a dietary inhibitor of iron absorption. These data indicate that OPN can function as an iron carrier for use in alternative strategies for delivering iron in a bioavailable form for intestinal uptake.
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spelling doaj-art-5ff44f71b5fe44d2b68dac62401e479f2025-08-20T02:39:08ZengElsevierJournal of Dairy Science0022-03022025-01-0110819010010.3168/jds.2024-25305Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cellsEmilie H. Buhl0Brian Christensen1Freja H. Pedersen2Esben S. S⊘rensen3Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, DenmarkDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, DenmarkDepartment of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, DenmarkCorresponding author; Department of Molecular Biology and Genetics, Aarhus University, 8000 Aarhus C, DenmarkABSTRACT: Insufficient absorption of iron and the consequent development of iron deficiency have serious health consequences. Hence, identification and development of iron delivery systems that can increase the bioavailability and uptake of dietary iron are important. Osteopontin (OPN) is an acidic and highly phosphorylated integrin-binding protein found in milk where it exists as a full-length protein and as N-terminally derived fragments. Milk OPN can be taken up by enterocytes and transported across the intestinal barrier into the circulation. Milk OPN has previously been shown to bind calcium and magnesium. This study investigates milk OPN as a carrier of iron and its potential to increase iron absorption in intestinal cells. Full-length OPN and N-terminal fragments of OPN were shown to bind ∼30 and ∼10 mol of iron, respectively, and the phosphorylated residues were crucial for iron binding. Osteopontin retained iron bound after simulated gastrointestinal digestion. Immunodetection of digested OPN and OPN-Fe complexes showed that the OPN-Fe complexes were more resistant to pepsin digestion than OPN without bound iron. The cellular uptake of iron was investigated by measuring intracellular ferritin formation and mRNA expression of divalent metal transporter 1 in Caco-2 cells. Osteopontin increased the uptake of iron even in the presence of phytic acid, a dietary inhibitor of iron absorption. These data indicate that OPN can function as an iron carrier for use in alternative strategies for delivering iron in a bioavailable form for intestinal uptake.http://www.sciencedirect.com/science/article/pii/S0022030224012359osteopontiniron bindingiron absorptionbioavailability
spellingShingle Emilie H. Buhl
Brian Christensen
Freja H. Pedersen
Esben S. S⊘rensen
Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells
Journal of Dairy Science
osteopontin
iron binding
iron absorption
bioavailability
title Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells
title_full Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells
title_fullStr Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells
title_full_unstemmed Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells
title_short Milk osteopontin has high iron-binding capacity and facilitates iron absorption in intestinal cells
title_sort milk osteopontin has high iron binding capacity and facilitates iron absorption in intestinal cells
topic osteopontin
iron binding
iron absorption
bioavailability
url http://www.sciencedirect.com/science/article/pii/S0022030224012359
work_keys_str_mv AT emiliehbuhl milkosteopontinhashighironbindingcapacityandfacilitatesironabsorptioninintestinalcells
AT brianchristensen milkosteopontinhashighironbindingcapacityandfacilitatesironabsorptioninintestinalcells
AT frejahpedersen milkosteopontinhashighironbindingcapacityandfacilitatesironabsorptioninintestinalcells
AT esbenssrensen milkosteopontinhashighironbindingcapacityandfacilitatesironabsorptioninintestinalcells