The long-term objective of the proposed research is to understand the physical chemistry of cariogenesis and to apply this knowledge to the prevention of caries. The initiation of a carious lesion is triggered by processes at the tooth-saliva interface (acid production by bacterial plaque) which modify the composition of the aqueous phase (i.e., plaque fluid) in contact with the enamel mineral. An important constituent of the interface is the acquired pellicle, presumably formed by selective adsorption of salivary macromolecules; the pellicle constitutes a natural defense against enamel demineralization but little is known about its actual formation mechanism. Remineralization of incipient caries should be related to the degree of supersaturation that the plaque fluid can reach with respect to the enamel mineral or with respect to basic calcium phosphates that can be incorporated within the enamel structure; this situation is expected to be modulated by the properties of the enamel-saliva interface. This research proposal, intended to elucidate these points, includes the following areas: 1. Adsorption from mixtures of salivary macromolecules onto hydroxyapatite, HA. Applicability of kinetic and thermodynamic models. 2. Interaction of adsorbed macromolecules onto HA with other adsorbates. Role of hydrophobicity in adsorbate-adsorbate condensation. 3. Adsorption thermodynamics of specific fragments (enzymatically obtained) from salivary macromolecules onto HA to elucidate the role of sequences and functional groups in adsorption. 4. Inhibition of HA crystal growth by salivary macromolecules, their fragments, and smaller molecules. Relationship between inhibitors activity and their adsorption behavior. 5. Saturation status of plaque fluid with respect to enamel and its changes with acidity. 6. The use of thermodynamic models (under controlled kinetics) to explain caries formation. Application of these models to the case of enamel remineralization in the presence of acquired pellicle (use of extracted teeth and synthetic HA surfaces. Areas 1, 2, and 3 will lead to a better understanding of pellicle formation and areas 4, 5 and 6 address the question of the caries process and the remineralization of incipient carious lesions.

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 #
5R37DE003187-24
Application #
2128891
Study Section
Special Emphasis Panel (NSS)
Project Start
1977-05-01
Project End
1996-04-30
Budget Start
1995-05-01
Budget End
1996-04-30
Support Year
24
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Forsyth Institute
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02142
Margolis, H C; Zhang, Y P; Lee, C Y et al. (1999) Kinetics of enamel demineralization in vitro. J Dent Res 78:1326-35
Smith, C E (1998) Cellular and chemical events during enamel maturation. Crit Rev Oral Biol Med 9:128-61
Smith, C E; Issid, M; Margolis, H C et al. (1996) Developmental changes in the pH of enamel fluid and its effects on matrix-resident proteinases. Adv Dent Res 10:159-69
Margolis, H C; Moreno, E C (1994) Composition and cariogenic potential of dental plaque fluid. Crit Rev Oral Biol Med 5:1-25
Margolis, H C; Zhang, Y P; Gewirtz, A et al. (1993) Cariogenic potential of pooled plaque fluid from exposed root surfaces in humans. Arch Oral Biol 38:131-8
Margolis, H C; Zhang, Y P; van Houte, J et al. (1993) Effect of sucrose concentration on the cariogenic potential of pooled plaque fluid from caries-free and caries-positive individuals. Caries Res 27:467-73
Tanaka, M; Moreno, E C; Margolis, H C (1993) Effect of fluoride incorporation into human dental enamel on its demineralization in vitro. Arch Oral Biol 38:863-9
Aoba, T; Shimoda, S; Moreno, E C (1992) Labile or surface pools of magnesium, sodium, and potassium in developing porcine enamel mineral. J Dent Res 71:1826-31
Margolis, H C; Moreno, E C (1992) Kinetics of hydroxyapatite dissolution in acetic, lactic, and phosphoric acid solutions. Calcif Tissue Int 50:137-43
Aoba, T; Moreno, E C; Shimoda, S (1992) Competitive adsorption of magnesium and calcium ions onto synthetic and biological apatites. Calcif Tissue Int 51:143-50

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