title: Casein phosphopeptides promote calcium uptake and modulate the differentiation pathway in human primary osteoblast-like cells.
abstract: Casein phosphopeptides (CPPs), originating by in vitro and/or in vivo casein digestion, are characterized by the ability to complex and solubilize calcium ions preventing their precipitation. Previous works demonstrated that CPPs improve calcium uptake by human differentiated intestinal tumor cell lines, are able to re-mineralize carious lesions in a dental enamel, and, as components of a diet, affect bone weight and calcium content in rats. The aim of the present study was to evaluate if CPPs can directly modulate bone cells activity and mineralization. Primary human osteoblast-like cells were established in culture from trabecular bone samples obtained from waste materials during orthopedic surgery. Commercial mixtures of bovine casein phosphopeptides were used. The CPP dependent intracellular calcium rises were monitored at the single cell level through fura2-fluorescence assays. Results show that CPPs: (i) stimulate calcium uptake by primary human osteoblast-like cells; (ii) increase the expression and activity of alkaline phosphatase, a marker of human osteoblast differentiation; (iii) affect the cell proliferation rate and the apoptotic level; (iv) enhance nodule formation by human SaOS-2. Taken together these results confirm the possibility that CPPs play a role as modulator of bone cell activity, probably sustained by their ability as calcium carriers. Although the exact mechanism by which CPPs act remains not completely clarified, they can be considered as potential anabolic factors for bone tissue engineering.
authors.affiliation: Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università degli Studi di Milano, LITA, Via Fratelli Cervi 93, 20090 Segrate, Italy.
authors.forename: Bianca Maria
authors.initials: BM
authors.lastname: Donida
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mrak
authors.forename: Claudia
authors.initials: C
authors.lastname: Gravaghi
authors.forename: Isabella
authors.initials: I
authors.lastname: Villa
authors.forename: Stefania
authors.initials: S
authors.lastname: Cosentino
authors.forename: Elena
authors.initials: E
authors.lastname: Zacchi
authors.forename: Silvia
authors.initials: S
authors.lastname: Perego
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rubinacci
authors.forename: Amelia
authors.initials: A
authors.lastname: Fiorilli
authors.forename: Guido
authors.initials: G
authors.lastname: Tettamanti
authors.forename: Anita
authors.initials: A
authors.lastname: Ferraretto
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002364:Caseins / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010748:Phosphopeptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
chemical_list: D002364:Caseins; D010748:Phosphopeptides; D007770:L-Lactate Dehydrogenase; D000469:Alkaline Phosphatase; D002118:Calcium