Milk osteopontin may promote brain development via up‐regulating osteopontin expression in vivo

Abstract

Osteopontin (OPN) is a highly acidic phosphorylated glycoprotein that is involved in a wide range of biological processes, including biomineralization, immune modulatory functions, cell survival and proliferation. OPN is abundantly expressed in the brain and has been suggested to play a role in brain development. OPN is present in high concentration in human milk. In mice, OPN is also expressed in the mammary gland and secreted in milk. However, the functions of milk OPN remain unclear. In this study, wild‐type and OPN knock‐out mice were used to investigate the influence of milk OPN on brain development. To examine if dietary OPN can be absorbed and transferred to the brain, day 20 wild‐type mouse pups were fed I‐125 labeled OPN via oral gavage. Brain radioactivity was measured by gamma counter. After 30 min, 1h and 2h of incubation, radioactivity in the brain was detected at a stable level, around 1.7% of total OPN fed. Two groups, a control and an OPN‐deficient group, were then used to investigate the effects of dietary OPN on brain development. Wild‐type mouse pups were either fed by wild‐type dams (control) or by OPN knock‐out dams (OPN‐deficient group). Brain samples were collected every other day from D1 to D20. OPN mRNA expression was similar from D1 to D20 in both groups. Immunoblotting showed that peak OPN expression occurred at D4, D6 and D8 in both groups, but the control group expressed significantly higher concentrations of OPN compared with the OPN‐deficient group, suggesting post‐transcriptional regulation In addition, genes involved in brain development, including glial cell differentiation regulator and proteolipid protein were up‐regulated in the control group. In conclusion, milk OPN may play a role in brain development during early life. Supported by Mead Johnson Nutrition.