Milk osteopontin promotes brain development by up‐regulating osteopontin in the brain in early life

Abstract

Osteopontin (OPN) is a pleiotropic protein and is abundantly present in milk. Its functions include immune modulation and cellular proliferation and differentiation. OPN is highly expressed in the brain. We investigated the effects of milk-derived OPN on brain development of mouse pups. Wild-type (WT) dams producing OPN milk and OPN knockout (KO) dams producing OPN milk nursed WT pups (OPN), yielding 2 pup treatment groups, OPN OPN and OPN OPN, for comparison. Preliminary studies supported use of this model by showing high concentrations of OPN in milk of WT dams and no OPN in milk of OPN KO dams, and production of similar amounts of milk by WT and KO dams. The ability of ingested milk OPN to enter the brain was revealed by appearance of orally gavaged [I]-labeled and antibody-probed milk OPN in brains of pups. Brain OPN mRNA levels were similar in both nursed groups, but the brain OPN protein level was significantly lower in the OPN OPN group at postnatal days 6 and 8. Behavior tests showed impaired memory and learning ability in OPN OPN pups. In addition, our study revealed increased expression of myelination-related proteins and elevated proliferation and differentiation of NG-2 glia into oligodendrocytes in the brain of OPN OPN pups, accompanied by increased activation of ERK-1/2 and PI3K/Akt signaling. We concluded that milk OPN can play an important role in brain development and behavior in infancy by promoting myelination.-Jiang, R., Prell, C., Lönnerdal, B. Milk osteopontin promotes brain development by up-regulating osteopontin in the brain in early life.

FAM20C phosphorylation of the RGDSVVYGLR motif in osteopontin inhibits interaction with the αvβ3 integrin

“…13,14 OPN plays prominent roles in many physiological processes including immunological responses, regulation of biomineralization, brain development and tumorigenesis. 10,15,16 OPN binds the α v β 1 , α v β 3 , α v β 5 , α v β 6 , α 5 β 1 , and α 8 β 1 integrins via the RGD sequence, 10,11 whereas the cryptic SVVYGLR sequence mediates interaction with the α 4 β 1 and α 9 β 1 integrins. 17,18 Phosphorylation of OPN can regulate the interaction with integrins.…”

Early-Life Supplementation of Bovine Milk Osteopontin Supports Neurodevelopment and Influences Exploratory Behavior

“…Breasting-feeding has been shown to have beneficial effects not only on overall growth performance and gut health, but also on brain growth and health [16,17], and the role of milk OPN on brain development has been a topic of interest in recent literature. Milk OPN has been found to pass the blood-brain barrier in mouse pups, where it significantly increased the expression of myelination-related proteins such as myelin basic protein and myelin-associated glycoprotein [18]. Whereas dietary milk-derived OPN has not been studied in this context, endogenous OPN synthesis has been shown to play an important role in re-myelination for neurodegenerative diseases such as Alzheimer's disease [19], and brain astrocytes have been shown to upregulate expression of OPN during re-myelination processes in mice, suggesting it may be involved in a repair-related role [20].…”

“…Although various studies have been performed to examine the effects of dietary OPN on immune functions, gut health and myelination during early life, the influence of bovine milk OPN on neonatal brain and cognitive development, especially during infancy, has not been extensively studied until recently [18,23]. Thus, the objective of the present study was to assess the effects of bovine milk OPN supplementation on neonatal brain and cognitive development using the translational pig model.…”

SPP1 Promotes Schwann Cell Proliferation and Survival through PKCα by Binding with CD44 and αvβ3 after Peripheral Nerve Injury

“…This self-sustainability is an important function in both remyelination and nerve regeneration [56]. By binding to membranous receptors, SPP1 stimulates proliferation and differentiation of NG-2 glial cells into oligodendrocytes by activating the ERK and PI3K/Akt signaling pathways [57]. And other study identi ed that SPP1 stimulated multiple myeloma cell proliferation through binding to CD44 and was involved in migration through binding to CD44 or αvβ3 [58].…”