Bone is characterized by a physiologic turnover, in adult too: 0.05% of calcium, about 500 mg/die, is daily removed (osteoclastic activity) and hidden (osteoblastic activity). This mean that, in the adult, in about six years all bone minerals is changed. Bone mass level remain the same when deposition rate is equal to reabsorption rate, that is when osteoclastic and osteoblastic activity are in equilibrium. This turnover is most fast in the infant, in this population all bone minerals is changed in about one year. About the total bone mass (Peak Bone Mass, PBM) is stored up within 18-20 years old. An inadequate intake of calcium in this period may lead to a low bone mineral density, which may have implications for bone health, notably risk of osteoporosis, in later life. The PBM attainment constitutes a very important goal: grater bone mass in adult life means lower fractures in old age. Calcium is an essential aliment: all calcium in the body comes from diet. Many foods contain calcium, but the amount of calcium, provided per 100 g or per serving, and is bioavailability vary considerably. The major source of calcium is milk and milk products. The high bioavailability of calcium in milk is essential due to the presence of caseinphosphopeptides, CPPs, bioactive peptides which are formed by proteolytic digestium of casein in the ileum. Thanks to the presence, in their aminoacidic sequence, of an “acidic motive”, constitutes by three phosphorilated serine and two glutammate, Ser(P)-Ser(P)-Ser(P)-Glu-Glu, these peptides are able to prevent the formation of insoluble Ca-phosphate precipitates in the intestinal by complexing ionized calcium in soluble chelates which enhance the amount of intraluminal calcium available for transport across the mucosa by the non-saturable pathway. Many searchers have proved their ability to increase the amount of calcium absorption and its utilization in bone tissue. Nevertheless, specially in humans searchers have not only obtained positive but also non-significant results. Long term clinical studies are necessary to better investigate CPPs role in humans. More positive results are obtained in oral health: pre-formed CPPs and amorphous calcium phosphate nanocomplex (CPP-APC) have the potential to provide superior clinical efficacy in preventing dental caries, treating and reparing early stage of disease. In present study we are demostrated that CPPs are able to iduce calcium uptake in osteoblasts, likewise they do in intestinal cells, both cell types involved in calcium metabolism in vivo. CPPs have instead no action in other cell types, like fibroblasts or neuronal cells. In particular, in osteoblast, kinetics and morphology CPPs cells response are different versus intestinal cells. This difference can be explained by different functions that they are assigned in vivo: intestinal cells are delegated to the calcium absorption instead osteoblast cells are delegated to the right calcemia maintenance. Moreover, in osteoblasts, CPPs action is mediated by L-type calcium channel activation and this calcium influx in response to CPPs somministration activates cellular function, such as differenziating activity to mature osteoblasts stadium, likewise in the presence of vitamin D3, osteoblasts lineage physiological growth factor. This results allow to suppose a role for CPPs not only as a functional food, as integration in prevention strategy of these pathologys and life styles characterized by an inadeguate calcium absorption and intake; but also as possible candidates in bone tissue engineering clinical strategies, for example by their integration in scaffolds. Nevertheless this is only the first step and more studies are necessary to better understand CPPs biological role and effect in vivo. In last years many scientific reports have open the doors to a new research area, in which bioactive components from foods are the protagonists. They not only contribute to as adequate nutritional value, but generate advantages for health, reducing the risk to untle several pathologys, without the contribution of body foreign chemical substances.

L'importanza del calcio e i caseinofosfopeptidi: dalla nutrizione all'ingegneria tissutale / B.m. Donida ; M. A. Pagani, G. Tettamanti, A. Ferraretto. DIPARTIMENTO DI CHIMICA, BIOCHIMICA E BIOTECNOLOGIE PER LA MEDICINA, DIPARTIMENTO DI SCIENZE E TECNOLOGIE ALIMENTARI E MICROBIOLOGICHE, 2009 Jan 21. 21. ciclo, Anno Accademico 2007/2008.

L'importanza del calcio e i caseinofosfopeptidi: dalla nutrizione all'ingegneria tissutale

B.M. Donida
2009

Abstract

Bone is characterized by a physiologic turnover, in adult too: 0.05% of calcium, about 500 mg/die, is daily removed (osteoclastic activity) and hidden (osteoblastic activity). This mean that, in the adult, in about six years all bone minerals is changed. Bone mass level remain the same when deposition rate is equal to reabsorption rate, that is when osteoclastic and osteoblastic activity are in equilibrium. This turnover is most fast in the infant, in this population all bone minerals is changed in about one year. About the total bone mass (Peak Bone Mass, PBM) is stored up within 18-20 years old. An inadequate intake of calcium in this period may lead to a low bone mineral density, which may have implications for bone health, notably risk of osteoporosis, in later life. The PBM attainment constitutes a very important goal: grater bone mass in adult life means lower fractures in old age. Calcium is an essential aliment: all calcium in the body comes from diet. Many foods contain calcium, but the amount of calcium, provided per 100 g or per serving, and is bioavailability vary considerably. The major source of calcium is milk and milk products. The high bioavailability of calcium in milk is essential due to the presence of caseinphosphopeptides, CPPs, bioactive peptides which are formed by proteolytic digestium of casein in the ileum. Thanks to the presence, in their aminoacidic sequence, of an “acidic motive”, constitutes by three phosphorilated serine and two glutammate, Ser(P)-Ser(P)-Ser(P)-Glu-Glu, these peptides are able to prevent the formation of insoluble Ca-phosphate precipitates in the intestinal by complexing ionized calcium in soluble chelates which enhance the amount of intraluminal calcium available for transport across the mucosa by the non-saturable pathway. Many searchers have proved their ability to increase the amount of calcium absorption and its utilization in bone tissue. Nevertheless, specially in humans searchers have not only obtained positive but also non-significant results. Long term clinical studies are necessary to better investigate CPPs role in humans. More positive results are obtained in oral health: pre-formed CPPs and amorphous calcium phosphate nanocomplex (CPP-APC) have the potential to provide superior clinical efficacy in preventing dental caries, treating and reparing early stage of disease. In present study we are demostrated that CPPs are able to iduce calcium uptake in osteoblasts, likewise they do in intestinal cells, both cell types involved in calcium metabolism in vivo. CPPs have instead no action in other cell types, like fibroblasts or neuronal cells. In particular, in osteoblast, kinetics and morphology CPPs cells response are different versus intestinal cells. This difference can be explained by different functions that they are assigned in vivo: intestinal cells are delegated to the calcium absorption instead osteoblast cells are delegated to the right calcemia maintenance. Moreover, in osteoblasts, CPPs action is mediated by L-type calcium channel activation and this calcium influx in response to CPPs somministration activates cellular function, such as differenziating activity to mature osteoblasts stadium, likewise in the presence of vitamin D3, osteoblasts lineage physiological growth factor. This results allow to suppose a role for CPPs not only as a functional food, as integration in prevention strategy of these pathologys and life styles characterized by an inadeguate calcium absorption and intake; but also as possible candidates in bone tissue engineering clinical strategies, for example by their integration in scaffolds. Nevertheless this is only the first step and more studies are necessary to better understand CPPs biological role and effect in vivo. In last years many scientific reports have open the doors to a new research area, in which bioactive components from foods are the protagonists. They not only contribute to as adequate nutritional value, but generate advantages for health, reducing the risk to untle several pathologys, without the contribution of body foreign chemical substances.
21-gen-2009
Settore AGR/15 - Scienze e Tecnologie Alimentari
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
FERRARETTO, ANITA
TETTAMANTI, GUIDO
PAGANI, MARIA AMBROGINA
Doctoral Thesis
L'importanza del calcio e i caseinofosfopeptidi: dalla nutrizione all'ingegneria tissutale / B.m. Donida ; M. A. Pagani, G. Tettamanti, A. Ferraretto. DIPARTIMENTO DI CHIMICA, BIOCHIMICA E BIOTECNOLOGIE PER LA MEDICINA, DIPARTIMENTO DI SCIENZE E TECNOLOGIE ALIMENTARI E MICROBIOLOGICHE, 2009 Jan 21. 21. ciclo, Anno Accademico 2007/2008.
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