Basic Biological Sciences Relationship between Concentration of Human Salivary Statherin and Inhibition of Calcium Phosphate Precipitation in Stimulated Human Parotid Saliva

Abstract

Human salivary secretions are supersaturated with respect to the calcium phosphate salts which form dental enamel, a property which provides important protection for the teeth. We previously proposed that statherin, a 43-residue phosphopeptide, plays a key role in this protective system by inhibiting or delaying potentially harmful precipitation of calcium phosphate salts in the salivary glands and mouth. The purpose of the present study was to determine if the concentrations of statherin in saliva, despite their wide normal range, are high enough to fulfill this function. Concentrations of statherin in stimulated human parotid saliva samples from 36 female and 32 male subjects, aged from 17 to 30 years, were determined by a single radial immunodiffusion method. Values found ranged from 3.0 to greater than 27.3 microM, with a mean value of 12.8 (S.D. +/- 5.46) microM. At concentrations below these values, statherin inhibited spontaneous precipitation of calcium phosphate salts from an assay system which was more supersaturated with respect to dicalcium phosphate dihydrate, and comparably supersaturated with respect to hydroxyapatite, than were human saliva samples. The inhibitory activities of five of the 65 stimulated parotid saliva samples assayed were greater than would be anticipated from their statherin concentrations. This unexplained discrepancy is not associated with the presence of the acidic proline-rich proteins in saliva, although these proteins also affect calcium phosphate precipitation. The results of this study show that statherin is present in stimulated human parotid saliva at concentrations and levels of activity which are consistent with its proposed biological function, and support the proposal that statherin plays a significant role in a system which provides a protective and reparative but stable environment for the teeth.

Chemical alteration by tooth bleaching of human salivary proteins that infiltrated subsurface enamel lesions —Experimental study with bovine lesion model systems—

“…The key activity of statherin is thought to be prevention of the spontaneous and undesirable precipitation of calcium phosphate in salivary gland ducts and on tooth surfaces as dental calculi 26) . The extremely high affinity of statherin to calcium phosphate likely inhibits any undesirable precipitation 27) . Due to the high affinity, statherin likely hinders remineralization of subsurface lesions by masking HA binding sites for crystal growth.…”

Intrinsically Disordered Proteins in Biomineralization

“…Statherin is an inhibitor of the nucleation and growth of HA in the supersaturated environment of saliva (Hay et al, 1984;Johnsson et al, 1991;Stayton et al, 2003). The Nterminal region of statherin contains highly acidic motifs (DSpSpEE, where Sp indicates a phosphoseryl residue), which are important for adsorption of statherin onto the surface of HA and the inhibition of HA growth (Raj et al, 1992).…”

Saliva-Bacterium Interactions in Oral Microbial Ecology

“…The fate of a specific salivary component once secreted into the oral cavity depends on its susceptibility to enzymatic attack, especially in the face of the numerous bacterial hydrolytic enzymes present in saliva (Nakamura and Slots, 1983;Zambon et al, (Mandel, 1980); amylase (Aguirre et al, 1987); cystatin (Aguirre et al, 1992); fibronectin (Babu and Dabbous, 1986;Tynelius-Bratthall et al, 1986); histatins (MacKay et al, 1984b); IgG (Cole et aL., 1978;Mandel, 1980); lactoferrin (Mandel, 1980;Rudney et al, 1991); lysozyme (Mandel, 1980;Rudney et al, 1991); MG2 (Aguirre et aL., 1993); f-2-microglobulin (Ericson et al, 1982); parotid agglutinin (Ericson and Rundegren, 1983); proline-rich proteins (Hay and Moreno, 1987;Kousvelari et al, 1980, Aguirre et al, 1993; sigA (Aguirre et al, 1987;Cole et al, 1978;Rudney et al, 1991;Stuchell and Mandel, 1978); statherin (Hay et al, 1984); transferrin (Mandel, 1980 . Unfortunately, little information exists regarding the susceptibility of individual salivary proteins to proteolytic degradation in the oral environment.…”