Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università degli Studi di Milano, LITA, Via Fratelli Cervi 93, 20090 Segrate, Italy.
Peptides. 2009 Dec;30(12):2233-41. doi: 10.1016/j.peptides.2009.08.003. Epub 2009 Aug 12.
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.
酪蛋白磷酸肽（CPPs），来源于体外和/或体内酪蛋白消化，其特点是能够络合和溶解钙离子，防止其沉淀。先前的研究表明，CPPs 可以提高人源分化肠肿瘤细胞系对钙的摄取，能够重新矿化牙釉质的龋损，并作为饮食的组成部分，影响大鼠的骨重量和钙含量。本研究旨在评估 CPPs 是否可以直接调节骨细胞的活性和矿化作用。原代人成骨样细胞是从骨科手术中废弃的骨组织中分离出来的。使用了商业混合的牛酪蛋白磷酸肽。通过 fura2 荧光法在单细胞水平上监测 CPP 依赖性细胞内钙升高。结果表明 CPPs：（i）刺激原代人成骨样细胞摄取钙；（ii）增加碱性磷酸酶的表达和活性，碱性磷酸酶是人类成骨分化的标志物；（iii）影响细胞增殖率和凋亡水平；（iv）增强人 SaOS-2 的结节形成。综上所述，这些结果证实了 CPPs 作为骨细胞活性调节剂的可能性，可能与其作为钙载体的能力有关。尽管 CPPs 作用的确切机制尚不完全清楚，但它们可以被认为是骨组织工程的潜在合成代谢因子。
