Our recent research has established that a system exists in human saliva which plays an important role in the maintenance, protection and repair of dental enamel. The key features of this system are the presence in saliva of, firstly, supersaturated but stabilized concentrations of calcium and phosphate ions, and secondly, two kinds of salivary macromolecules which stabilize the supersaturated saliva by inhibiting precipitation of calcium phosphate salts. The supersaturated saliva provides important protection for the teeth by providing driving forces which, firstly, stabilize the enamel mineral, secondly, oppose enamel dissolution and mineral transport during carious attack of the teeth, and, thirdly, provides a mechanism for the repair of many early carious lesions. The precipitation inhibitors control this supersaturation by, firstly, preventing precipitation of calcium phosphate salts in the salivary glands and the oral cavity, and secondly, because they inhibit crystal growth of calcium phosphate salts, they prevent unwanted accretion of mineral onto the tooth surface. Significantly, their mechanisms of action do not affect calcium and phosphate ion activities in the saliva. Also, it is probable that one or both of the inhibitors contribute to the formation of the acquired enamel pellicle, a protein integument present on the enamel surface which provides significant protection for the teeth. The purpose of the proposed research is to elucidate the mechanisms by which the precipitation inhibitors act, both in terms of their molecular structures, which are now partly known, and in terms of their post-secretion behavior in the oral cavity. In addition, we propose to establish their broad biological significance by studying species other than human, particularly sub-human primates and laboratory animals used for dental caries and periodontal disease research. From this research will come an improved understanding of important relationships which exist between the teeth and their oral environment, both in health and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
4R37DE003915-19
Application #
3482732
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-07-01
Project End
1997-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
19
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02142
Hay, D I (1995) Salivary factors in caries models. Adv Dent Res 9:239-43
Schlesinger, D H; Hay, D I; Schluckebier, S K et al. (1994) Primary structure of a novel human salivary acidic proline-rich protein. Pept Res 7:242-7
Hay, D I; Ahern, J M; Schluckebier, S K et al. (1994) Human salivary acidic proline-rich protein polymorphisms and biosynthesis studied by high-performance liquid chromatography. J Dent Res 73:1717-26
Schwartz, S S; Hay, D I; Schluckebier, S K (1992) Inhibition of calcium phosphate precipitation by human salivary statherin: structure-activity relationships. Calcif Tissue Int 50:511-7
Gibbons, R J; Hay, D I; Schlesinger, D H (1991) Delineation of a segment of adsorbed salivary acidic proline-rich proteins which promotes adhesion of Streptococcus gordonii to apatitic surfaces. Infect Immun 59:2948-54
Spielman, A I; Bernstein, A; Hay, D I et al. (1991) Purification and characterization of a rabbit salivary protein, a potent inhibitor of crystal growth of calcium phosphate salts. Arch Oral Biol 36:55-63
Kishimoto, E; Hay, D I; Gibbons, R J (1989) A human salivary protein which promotes adhesion of Streptococcus mutans serotype c strains to hydroxyapatite. Infect Immun 57:3702-7
Gibbons, R J; Hay, D I (1989) Adsorbed salivary acidic proline-rich proteins contribute to the adhesion of Streptococcus mutans JBP to apatitic surfaces. J Dent Res 68:1303-7
Schlesinger, D H; Hay, D I; Levine, M J (1989) Complete primary structure of statherin, a potent inhibitor of calcium phosphate precipitation, from the saliva of the monkey, Macaca arctoides. Int J Pept Protein Res 34:374-80
Hay, D I; Bennick, A; Schlesinger, D H et al. (1988) The primary structures of six human salivary acidic proline-rich proteins (PRP-1, PRP-2, PRP-3, PRP-4, PIF-s and PIF-f). Biochem J 255:15-21

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