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Lecture 49Department of Biochemistry and Molecular Biology

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Title: Lecture 49Department of Biochemistry and Molecular Biology


1
Saliva and Dental CariesM. Lenander-Lumikari.
V. LoimarantaDepartment of Cariology and Turku
Immunology Centre, Institute ofDentistry,
University of Turku, Lemminkaisenkatu 2, FIN -
20520 Turku,Finland, Corresponding author,
marlen_at_utu.fiAdv Dent Res 1440-47, December,
2000
  • Caries is a unique multifactorial infectious
    disease. Our understanding of etiological
    factors, the progress of the disease, and the
    effectiveness of prophylactic procedures have led
    us to believe that we understand the disease.
    However, we still have too few answers to many
    questions "Why can we not predict who will get
    the disease?" "Why do we not become immunized?"
    "How much saliva is enough?" or "Which salivary
    components are protective?" and "Which salivary
    components predispose for caries?" It is
    generally accepted, however, that saliva
    secretion and salivary components secreted in
    saliva are important for dental health. The final
    result, "caries to be or not to be", is a complex
    phenomenon involving internal defense factors,
    such as saliva, tooth surface morphology, general
    health, and nutritional and hormonal status, and
    a number of external factors-for example, diet,
    the microbial flora colonizing the teeth, oral
    hygiene, and fluoride availability. In this
    article, our aim is to focus on the effects of
    saliva and salivary constituents on cariogenic
    bacteria and the subsequent development of dental
    caries.

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3
Section of a human molar
4
Cavity
5
Cells producing dentin and enamel
6
Higher magnification view of ameloblasts
7
Higher magnification view of odontoblasts
8
Localization of macromolecules associated with
calcification in mammals
9
Organic Components of Calcified Tissues
10
Dentin Proteins
  • Collagen type I
  • FGF beta Occurs in dentine in inactive form and
    is activated during active dentin formation
  • Osteopontin Highly acidic glycoprotein of MW
    44,000-probably binds Ca during calcification.
  • OsteonectinOsteonectin is a glycoprotein in the
    bone that binds calcium. It is secreted by
    osteoblasts and odontoblasts initiating
    mineralization and promoting mineral crystal
    formation. Osteonectin also shows affinity for
    collagen in addition to bone mineral calcium
  • Osteogenin Also known as bone morphogenic
    protein
  • OsteocalcinOsteocalcin is a noncollagenous
    protein found in bone and dentin. It is secreted
    by osteoblasts and thought to play a role in
    mineralization and calcium ion homeostasis. It
    has been stipulated that osteocalcin may also
    function as a negative regulator of bone
    formation, although its exact role is unknown.
  • Dentin specific proteins

11
Dentin Specific proteins
  • Several extracellular matrix (ECM) proteins have
    been isolated from dentin and shown to be
    synthesized by odontoblasts.
  • Highly phosphorylated proteins (HP), the
    phosphophoryns, are specifically found in dentin
    and are synthesized only by odontoblasts.
    Phosphophoryns are probably involved in
    controlling the site and/or the rate of
    circumpulpal mineralization.
  • Other moderately phosphorylated (MP) and low
    phosphorylated (LP) proteins have also been
    detected in dentin, but have not been studied
    extensively.

12
Enamel Proteins
  • Ameloblastin the function of ameloblastins is
    believed to be in controlling the elongation of
    enamel crystals and generally directing enamel
    mineralization during tooth development.
  • Amelogenin The latest research indicates that
    this protein regulates the initiation and growth
    of hydroxyapatite crystals during the
    mineralization of enamel. In addition,
    amelogenins appear to aid in the development of
    cementum by directing cells that form cementum to
    the root surface of teeth.

13
Enamel Proteins------
  • The genes for amelogenin can be used in sex
    determination of samples from unknown human
    origin. Using primers specific for intron I of
    this gene, PCR amplification of the X chromosome
    gives a 106 bp fragment and Y chromosome gives a
    112 bp fragment.

Male
Female
14
Tuftelin
  • Tuftelin is an acidic phosphorylated
    glycoproteinfound in tooth enamel. This protein
    is formed for a short time during amelogenesis.
    The function of tuftelins is under contention,
    but it is proposed that it acts to start the
    mineralization process of enamel during tooth
    developement

15
Enamelins
  • Enamelin is a protein found in developing tooth
    enamel. About 30 of developing enamel consists
    of protein of which enamelins comprise lt1.
    Enamelin is not a proteolytic enzyme and does not
    degrade other enamel proteins. Two enamelins of
    MW 63 and 67 Kda have been purified. These
    strongly bind to hydroxyapatite. Mechanism of
    their action is not clear.

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Ground Substance Organization
19
EM of Biofilm
20
Salivary Enzymes in Normal Function and Abnormal
Pathology
  • a-Amylasenormally present in salivaimportant in
    digestion
  • Lysozyme
  • Hyaluronidase
  • Chondrosulfatase
  • Aryl Sulfatase
  • Neutral Protease
  • Collagenases

21
Dental Caries
  • Parotid Gland
  • Lysozyme
  • Oral Microbe Cell Wall Polysaccharides
  • (polymers of NAG and NA-neuraminic acid)
  • Hyaluronidase
  • Mucinase
  • Chondrosulfatase
  • Arylsulfatase

22
Salivary Enzymes-Role in Dental Caries
  • Components of Dentine are
  • Organic matrix consisting of collagen,
    glycoproteins, proteoglycans, dentin specific
    proteins
  • Inorganic matrix consisting of hydroxyapatite
  • In Oral Cavity
  • Starch Dextrins
    Monosaccharides
  • a-amylase
    ß-amylase
  • Monosaccharides? Lactic acid under anaerobic
    glycolysis
  • Ca3(PO4)2 H 4 H2O? 3Ca(OH)2 2H3PO4

23
Functions of Released Enzymes
  • Components of dentinCollagen, Hyaluronic acid,
    Sulfated glycoproteins, Hydroxyapatite
  • Hyaluronic Acid NAG Glucuronic
    Acid
  • HU
  • Sulfated Glycoproteins NAG sulfate
    Glucuronic Acid
  • AS, CS

  • Acids produced breakdown the hydroxyapatite
    crystal lattice

24
Resorption of Organic matrix
  • Abnormal Dentin Structure
  • Exposed Collagen type I in a
  • Abnormal Hydroxyapatite Crystal lattice
  • Human Collagenase type I Bacterial
    collagenase
  • ¾ and ¼ Chains of collagen
  • Type IV Collagenase Neutral
    Proteinase
  • Amino acids and peptides

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Hormonal factors in Dental Caries
  • Salivary Clearance capacity-higher the
    flow-better flushing and lower caries levels
  • Antibiotics and other drugs decrease salivary
    flow rate-higher rate of caries
  • Salivary buffer effect-greater in men than in
    women women have higher incidence of caries
  • Post menopausal women have higher incidence of
    caries-hormone replacement therapy improves the
    condition
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