Casein phosphopeptides promote calcium uptake and modulate the differentiation pathway in human primary osteoblast-like cells

Donida, B.M.; Mrak, Emanuela; Gravaghi, Claudia; Villa, Isabella; Cosentino, S.; Zacchi, Elena; Perego, Silvia; Rubinacci, Alessandro; Fiorilli, Amelia; Tettamanti, Guido; Ferraretto, Anita

doi:10.1016/j.peptides.2009.08.003

Cited by 62 publications

(49 citation statements)

References 38 publications

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“…Consistent with the notion that their function is mainly nutritional (5,6), the sole site of expression was believed to be the mammary gland. The organization and orientation of the diverse casein genes within their genomic cluster is highly conserved (31).…”

Section: Discussionsupporting

confidence: 62%

“…In humans, they represent ∼30% of the protein fraction (3). Caseins were believed to mainly function as an amino acid source (4) and to ameliorate the uptake of trace elements and calcium from the intestine of infants (5,6). Polypeptides in milk may be degraded by proteases within milk and the digestive tract or survive the digestive process in an intact form (1).…”

mentioning

confidence: 99%

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Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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Caseins are major constituents of mammalian milks that are thought to be exclusively expressed in mammary glands and to function primarily as a protein source, as well as to ameliorate intestinal calcium uptake. In addition, proinflammatory and immunomodulatory properties have been reported for bovine caseins. Our aim was to investigate whether human casein α s1 (CSN1S1) is expressed outside the mammary gland and possesses immunomodulatory functions in humans as well. For this purpose, CSN1S1 mRNA was detected in primary human monocytes and CD4+ and CD8+ T cells, but not in CD19+ B cells. CSN1S1 protein was traceable in supernatants of cultured primary human CD14+ monocytes by ELISA. Similarly, CSN1S1 mRNA and protein were detected in the human monocytic cell lines HL60, U937, and THP1 but not in Mono Mac 6 cells. Moreover, permeabilized human monocytes and HL60 cells could be stained by immunofluorescence, indicating intracellular expression. Recombinant human CSN1S1 was bound to the surface of Mono Mac 6 cells and upregulated the expression of GM-CSF mRNA in primary human monocytes and Mono Mac 6 cells in a time- and concentration-dependent manner. A similar increase in GM-CSF protein was found in the culture supernatants. CSN1S1-dependent upregulation of GM-CSF was specifically blocked by the addition of the p38 MAPK inhibitor ML3403. Our results indicated that human CSN1S1 may possess an immunomodulatory role beyond its nutritional function in milk. It is expressed in human monocytes and stimulates the expression of the proinflammatory cytokine GM-CSF.

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Section: Discussionsupporting

confidence: 62%

mentioning

confidence: 99%

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Vordenbäumen

Braukmann

Petermann

et al. 2011

The Journal of Immunology

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show abstract

“…The possibility to use a calcium enriched CPP mixture, like the one here employed, forming very stable aggregates, regardless of the extracellular calcium concentration, could overcome these problems, and be of practical relevance when CPP aggregates should be used as functional foods or nutraceuticals (Bosscher, Van Caillie-Bertrand, Van Cawwenbergh, & Deelsdra, 2003;Gaucheron, Le Graet, Boyaval, & Piot, 1997). In this regard, it is worth noting that recent data from our laboratory have demonstrated that the same calcium enriched CPPs were more active in inducing the formation of mineralization nodules in osteoblast-like cells than a calcium free CPP mixture (Donida et al, 2009).…”

Section: Discussionmentioning

confidence: 92%

Calcium ions enclosed in casein phosphopeptide aggregates are directly involved in the mineral uptake by differentiated HT-29 cells

Cosentino

Donida

Marasco

et al. 2010

International Dairy Journal

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“…Casein phosphopeptides obtained by in vitro enzymatic hydrolysis of CN, have been shown to enhance calcium solubility (Reeves and Latour, 1958) and to increase the calcification of embryonic rat bones in their diaphyseal area (Gerber and Jost, 1986). Donida et al (2009) reported that a CN-derived hydrolysate containing CPP modulates calcium uptake and the differentiation pathways in human osteoblast-like cells. Tulipano et al (2010) demonstrated that CPP may directly affect osteoblast-like cell growth, calcium uptake, and ultimately calcium deposition in the extracellular matrix, either with stimulatory or inhibitory effects.…”

Section: Benefits From Milk: Some Experimental Detailsmentioning

confidence: 99%

Invited review: Dairy intake and bone health: A viewpoint from the state of the art

Caroli

Poli²,

Ricotta

et al. 2011

Journal of Dairy Science

142

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Casein phosphopeptides promote calcium uptake and modulate the differentiation pathway in human primary osteoblast-like cells

Cited by 62 publications

References 38 publications

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Casein α s1 Is Expressed by Human Monocytes and Upregulates the Production of GM-CSF via p38 MAPK

Calcium ions enclosed in casein phosphopeptide aggregates are directly involved in the mineral uptake by differentiated HT-29 cells

Invited review: Dairy intake and bone health: A viewpoint from the state of the art

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