The Interactions of CPP-ACP with Saliva

Noorjahan Laila Huq, Helen Myroforidis, Keith J Cross, David P Stanton, Paul D Veith, Brent R Ward, Eric C Reynolds, Noorjahan Laila Huq, Helen Myroforidis, Keith J Cross, David P Stanton, Paul D Veith, Brent R Ward, Eric C Reynolds

Abstract

The repair of early dental caries lesions has been demonstrated by the application of the remineralisation technology based on casein phosphopeptide-stabilised amorphous calcium phosphate complexes (CPP-ACP). These complexes consist of an amorphous calcium phosphate mineral phase stabilised and encapsulated by the self-assembly of milk-derived phosphopeptides. During topical application of CPP-ACP complexes in the oral cavity, the CPP encounters the enamel pellicle consisting of salivary proteins and peptides. However the interactions of the CPP with the enamel salivary pellicle are not known. The studies presented here reveal that the predominant peptides of CPP-ACP complexes do interact with specific salivary proteins and peptides of the enamel pellicle, and provide a mechanism by which the CPP-ACP complexes are localised at the tooth surface to promote remineralisation.

Keywords: casein phosphopeptide; enamel; pellicle; saliva.

Figures

Figure 1
Figure 1
The sequences of the two major casein tryptic phosphopeptides with the calcium phosphate binding-motif underlined are depicted using the three-letter code.
Figure 2
Figure 2
SDS-PAGE profile of salivary proteins derived from whole saliva (WS) bound to casein phosphopeptides (CPP)-coated or uncoated HA. Lane 1: Salivary proteins not bound to β-CN (1–25). Lane 2: Salivary proteins bound to β-CN (1–25). Lane 3: WS. Lane 4: Salivary proteins bound to αS1-CN (59–79). Lane 5: Salivary proteins not bound to αS1-CN (59–79). Lane 6: WS diluted 1 in 20. Lane 7: WS. Lane 8: Salivary proteins bound to uncoated HA control. Lane 9: Salivary proteins not bound to uncoated HA. Lane 10: Prestained markers.
Figure 3
Figure 3
Mass and pI distribution of salivary proteins and peptides of human acquired enamel pellicle that bind to CPP (αS1-CN (59–79), β-CN (1–25)).
Figure 4
Figure 4
ELISA of αS1-CN (59–79) binding to whole saliva (blue squares) and parotid saliva (red circles) and β-CN (1–25) binding to whole saliva (white diamonds).
Figure 5
Figure 5
ELISA of αS1-CN (59–79) (triangles) and β-CN (1–25) (squares) binding to (A) Histatin 1; (B) Statherin; (C) Amylase; (D) Albumin.

References

    1. Loesche W. Role of Streptococcus mutans in human dental decay. Microbiol. Rev. 1986;50:353–380.
    1. Featherstone J.D.B. Dental caries: A dynamic disease process. Aust. Dent. J. 2008;53:286–291. doi: 10.1111/j.1834-7819.2008.00064.x.
    1. Bradshaw D.J., Lynch R.J. Diet and the microbial aetiology of dental caries: New paradigms. Int. Dent. J. 2013;63:64–72. doi: 10.1111/idj.12082.
    1. Merritt J., Qi F., Shi W. Milk helps build strong teeth and promotes oral health. J. Calif. Dent. Assoc. 2006;34:361–366.
    1. Aimutis W.R. Bioactive properties of milk proteins with particular focus on anticariogenesis. J. Nutr. 2004;134:989S–995S.
    1. Reynolds E.C., Cain C.J., Webber F.L., Black C.L., Riley P.F., Johnson I.H., Perich J.W. Anticariogenicity of calcium phosphate complexes of tryptic casein phosphopeptides in the rat. J. Dent. Res. 1995;74:1272–1279. doi: 10.1177/00220345950740060601.
    1. Reeves R.E., Latour N.G. Calcium phosphate sequestering phosphopeptide from casein. Science. 1958;128:472. doi: 10.1126/science.128.3322.472.
    1. Swaisgood H.E. Chemistry of milk protein. Dev. Dairy Chem. 1982;1:1–59.
    1. Reynolds E.C., Cai F., Shen P., Walker G.D. Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum. J. Dent. Res. 2003;82:206–211. doi: 10.1177/154405910308200311.
    1. Cross K.J., Huq N.L., Palamara J.E., Perich J.W., Reynolds E.C. Physicochemical characterization of casein phosphopeptide-amorphous calcium phosphate nanocomplexes. J. Biol. Chem. 2005;280:15362–15369. doi: 10.1074/jbc.M413504200.
    1. Cochrane N.J., Saranathan S., Cai F., Cross K.J., Reynolds E.C. Enamel subsurface lesion remineralisation with casein phosphopeptide stabilised solutions of calcium, phosphate and fluoride. Caries Res. 2008;42:88–97. doi: 10.1159/000113161.
    1. Reynolds E.C. Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions. J. Dent. Res. 1997;76:1587–1595. doi: 10.1177/00220345970760091101.
    1. Cross K.J., Huq N.L., Reynolds E.C. Casein phosphopeptides in oral health—Chemistry and clinical applications. Curr. Pharm. Des. 2007;13:793–800. doi: 10.2174/138161207780363086.
    1. Reynolds E.C., Cai F., Cochrane N.J., Shen P., Walker G.D., Morgan M.V., Reynolds C. Fluoride and casein phosphopeptide-amorphous calcium phosphate. J. Dent. Res. 2008;87:344–348. doi: 10.1177/154405910808700420.
    1. Cochrane N.J., Cai F., Huq N.L., Burrow M.F., Reynolds E.C. New approaches to enhanced remineralization of tooth enamel. J. Dent. Res. 2010;89:1187–1197. doi: 10.1177/0022034510376046.
    1. Morgan M.V., Adams G.G., Bailey D.L., Tsao C.E., Fischman S.L., Reynolds E.C. The anticariogenic effect of sugar-free gum containing CPP-ACP nanocomplexes on approximal caries determined using digital bitewing radiography. Caries Res. 2008;42:171–184. doi: 10.1159/000128561.
    1. Yengopal V., Mickenautsch S. Caries preventive effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP): A meta-analysis. Acta Odontol. Scand. 2009;67:321–332. doi: 10.1080/00016350903160563.
    1. Cochrane N.J., Reynolds E.C. Calcium phosphopeptides—Mechanisms of action and evidence for clinical efficacy. Adv. Dent. Res. 2012;24:41–47. doi: 10.1177/0022034512454294.
    1. Lendenmann U., Grogan J., Oppenheim F.G. Saliva and dental pellicle-A review. Adv. Dent. Res. 2000;14:22–28. doi: 10.1177/08959374000140010301.
    1. Zimmerman J.N., Custodio W., Hatibovic-Kofman S., Lee Y.H., Xiao Y., Siqueira W.L. Proteome and peptidome of human acquired enamel pellicle on deciduous teeth. Int. J. Mol. Sci. 2013;14:920–934. doi: 10.3390/ijms14010920.
    1. Siqueira W.L., Zhang W.M., Helmerhorst E.J., Gygi S.P., Oppenheim F.G. Identification of protein components in in vivo human acquired enamel pellicle using LC-ESI-MS/MS. J. Proteome Res. 2007;6:2152–2160. doi: 10.1021/pr060580k.
    1. Siqueira W.L., Oppenheim F.G. Small molecular weight proteins/peptides present in the in vivo formed human acquired enamel pellicle. Arch. Oral Biol. 2009;54:437–444. doi: 10.1016/j.archoralbio.2009.01.011.
    1. Vitorino R., Calheiros-Lobo M.J., Duarte J.A., Domingues P.M., Amado F.M.L. Peptide profile of human acquired enamel pellicle using MALDI tandem MS. J. Sep. Sci. 2008;31:523–537. doi: 10.1002/jssc.200700486.
    1. Vitorino R., Calheiros-Lobo M.J., Williams J., Ferrer-Correia A.J., Tomer K.B., Duarte J.A., Domingues P.M., Amado F.M. Peptidomic analysis of human acquired enamel pellicle. Biomed. Chromatogr. 2007;21:1107–1117. doi: 10.1002/bmc.830.
    1. Vitorino R., de Morais Guedes S., Ferreira R., Lobo M.J., Duarte J., Ferrer-Correia A.J., Tomer K.B., Domingues P.M., Amado F.M. Two-dimensional electrophoresis study of in vitro pellicle formation and dental caries susceptibility. Eur. J. Oral Sci. 2006;114:147–153. doi: 10.1111/j.1600-0722.2006.00328.x.
    1. Vitorino R., Lobo M.J., Duarte J., Ferrer-Correia A.J., Tomer K.B., Dubin J.R., Domingues P.M., Amado F.M. In vitro hydroxyapatite adsorbed salivary proteins. Biochem. Biophys. Res. Commun. 2004;320:342–346. doi: 10.1016/j.bbrc.2004.05.169.
    1. Yao Y., Berg E.A., Costello C.E., Troxler R.F., Oppenheim F.G. Identification of protein components in human acquired enamel pellicle and whole saliva using novel proteomics approaches. J. Biol. Chem. 2003;278:5300–5308. doi: 10.1074/jbc.M206333200.
    1. Yao Y., Grogan J., Zehnder M., Lendenmann U., Nam B., Wu Z., Costello C.E., Oppenheim F.G. Compositional analysis of human acquired enamel pellicle by mass spectrometry. Arch. Oral Biol. 2001;46:293–303. doi: 10.1016/S0003-9969(00)00134-5.
    1. Cross K.J., Huq N.L., O’Brien-Simpson N.M., Perich J.W., Attard T.J., Reynolds E.C. The role of multiphosphorylated peptides in mineralized tissue regeneration. Int. J. Pept. Res. Ther. 2007;13:479–495. doi: 10.1007/s10989-007-9105-0.
    1. Huq N.L., Cross K.J., Ung M., Myroforidis H., Veith P.D., Chen D., Stanton D., He H., Ward B.R., Reynolds E.C. A review of the salivary proteome and peptidome and saliva-derived peptide therapeutics. Int. J. Pept. Res. Ther. 2007;13:547–564. doi: 10.1007/s10989-007-9109-9.
    1. Rölla G., Ekstrand J. Fluoride in oral fluids and dental plaque. In: Fejerskov O., Burt B.A., editors. Fluoride in Dentistry. Munksgaard; Copenhagen, Denmark: 1996. pp. 215–229.
    1. Jensen J.L., Lamkin M.S., Oppenheim F.G. Adsorption of human salivary proteins to hydroxyapatite: A comparison between whole saliva and glandular salivary secretions. J. Dent. Res. 1992;71:1569–1576. doi: 10.1177/00220345920710090501.
    1. Denny P., Hagen F.K., Hardt M., Liao L., Yan W., Arellanno M., Bassilian S., Bedi G.S., Boontheung P., Cociorva D., et al. The proteomes of human parotid and submandibular/sublingual gland salivas collected as the ductal secretions. J. Proteome Res. 2008;7:1994–2006. doi: 10.1021/pr700764j.
    1. Flora B., Gusman H., Helmerhorst E.J., Troxler R.F., Oppenheim F.G. A new method for the isolation of histatins 1, 3, and 5 from parotid secretion using zinc precipitation. Protein Expr. Purif. 2001;23:198–206. doi: 10.1006/prep.2001.1493.

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