Naturally Occurring N-Terminal Fragments of Bovine Milk Osteopontin Are Transported across Models of the Intestinal Barrier

Christensen, Brian; Nielsen, Nanna R.; Sørensen, Marie R.; Jacobsen, Lotte Neergaard; Ostenfeld, Marie Stampe; Sørensen, Esben S.

doi:10.3390/biomedicines11030893

Cited by 7 publications

(4 citation statements)

References 41 publications

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“…This development holds the potential to provide a more accurate biomarker for evaluating the risk of DKD in individuals with DM [15]. Another study, although in a different scenario, demonstrated that milk ntOPN bounded intestinal cells most effectively and was transported across the intestinal membrane indicating that proteolytic processing of OPN to form ntOPN increases its biological activity [273]. These findings support the efficacy of OPN/ntOPN as a therapeutic target in DKD.…”

Section: Opn-mediated Fibrosis In Dkdmentioning

confidence: 76%

Pathomechanisms of Diabetic Kidney Disease

Sinha,

Nicholas

2023

JCM

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The worldwide occurrence of diabetic kidney disease (DKD) is swiftly rising, primarily attributed to the growing population of individuals affected by type 2 diabetes. This surge has been transformed into a substantial global concern, placing additional strain on healthcare systems already grappling with significant demands. The pathogenesis of DKD is intricate, originating with hyperglycemia, which triggers various mechanisms and pathways: metabolic, hemodynamic, inflammatory, and fibrotic which ultimately lead to renal damage. Within each pathway, several mediators contribute to the development of renal structural and functional changes. Some of these mediators, such as inflammatory cytokines, reactive oxygen species, and transforming growth factor β are shared among the different pathways, leading to significant overlap and interaction between them. While current treatment options for DKD have shown advancement over previous strategies, their effectiveness remains somewhat constrained as patients still experience residual risk of disease progression. Therefore, a comprehensive grasp of the molecular mechanisms underlying the onset and progression of DKD is imperative for the continued creation of novel and groundbreaking therapies for this condition. In this review, we discuss the current achievements in fundamental research, with a particular emphasis on individual factors and recent developments in DKD treatment.

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Section: Opn-mediated Fibrosis In Dkdmentioning

confidence: 76%

Pathomechanisms of Diabetic Kidney Disease

Sinha,

Nicholas

2023

JCM

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“…Resistance to digestive proteases is primarily attributed to the glycosylated and conserved threonine residues close to the Arg-Gly-Asp integrin-binding sequence ( 44 , 54 , 57 , 58 ). In vitro evidence suggests that intact OPN and/or fragments can cross the intestinal barrier via transcytosis ( 59 ), and dietary bmOPN has been detected in the plasma of rodents and humans ( 23 , 55 , 60 ), demonstrating absorption.…”

Section: Absorption Distribution Metabolism and Excretion Of Milk Ost...mentioning

confidence: 99%

An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy

Fleming,

Reyes,

Donovan

et al. 2024

Front. Nutr.

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Human milk, due to its unique composition, is the optimal standard for infant nutrition. Osteopontin (OPN) is abundant in human milk but not bovine milk. The addition of bovine milk osteopontin (bmOPN) to formula may replicate OPN’s concentration and function in human milk. To address safety concerns, we convened an expert panel to assess the adequacy of safety data and physiological roles of dietary bmOPN in infancy. The exposure of breastfed infants to human milk OPN (hmOPN) has been well-characterized and decreases markedly over the first 6 months of lactation. Dietary bmOPN is resistant to gastric and intestinal digestion, absorbed and cleared from circulation within 8–24 h, and represents a small portion (<5%) of total plasma OPN. Label studies on hmOPN suggest that after 3 h, intact or digested OPN is absorbed into carcass (62%), small intestine (23%), stomach (5%), and small intestinal perfusate (4%), with <2% each found in the cecum, liver, brain, heart, and spleen. Although the results are heterogenous with respect to bmOPN’s physiologic impact, no adverse impacts have been reported across growth, gastrointestinal, immune, or brain-related outcomes. Recombinant bovine and human forms demonstrate similar absorption in plasma as bmOPN, as well as effects on cognition and immunity. The panel recommended prioritization of trials measuring a comprehensive set of clinically relevant outcomes on immunity and cognition to confirm the safety of bmOPN over that of further research on its absorption, distribution, metabolism, and excretion. This review offers expert consensus on the adequacy of data available to assess the safety of bmOPN for use in infant formula, aiding evidence-based decisions on the formulation of infant formula.

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“…In an in vitro study, the bovine milk OPN fragment Trp 27 -Phe 151 , generated by pepsin cleavage, was shown to cross models of the intestinal barrier via transcytosis [85]. The naturally occurring N-terminal OPN fragments bound intestinal cells more effectively and were more effectively transported across the membrane models compared to fulllength OPN.…”

Section: Digestion and Uptake Of Milk Osteopontinmentioning

confidence: 99%

Milk Osteopontin and Human Health

Sørensen

Christensen

2023

Nutrients

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Osteopontin (OPN) is a multifunctional protein found in all vertebrates. OPN is expressed in many different cell types, and is consequently found in most tissues and physiological secretions. OPN is involved in a multitude of biological processes, such as activation and regulation of the immune system; biomineralization; tissue-transformative processes, including growth and development of the gut and brain; interaction with bacteria; and many more. OPN is found in the highest concentrations in milk, where it is believed to initiate and regulate developmental, immunological and physiological processes in infants who consume milk. Processes for the isolation of bovine OPN for use in infant formula have been developed, and in recent years, many studies have investigated the effects of the intake of milk OPN. The purpose of this article is to review and compare existing knowledge about the structure and function of milk OPN, with a particular focus on the effects of milk OPN on human health and disease.

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Naturally Occurring N-Terminal Fragments of Bovine Milk Osteopontin Are Transported across Models of the Intestinal Barrier

Cited by 7 publications

References 41 publications

Pathomechanisms of Diabetic Kidney Disease

Pathomechanisms of Diabetic Kidney Disease

An expert panel on the adequacy of safety data and physiological roles of dietary bovine osteopontin in infancy

Milk Osteopontin and Human Health

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