Chemistry Reference
In-Depth Information
different descriptions of the tuftelin proteins, first described by Deutsch et al. (1989) and
there was significant disagreement in the data (Deutsch et al. 1998; MacDougall et al.
1998). Tuftelin mRNA has been detected in some non-dental tissues (MacDougall et al.
1998). Human tuftelin cDNA has been sequenced and shown to have an open reading
frame of 1170 bp, encoding a 390 amino acid protein with a calculated M
r
= 44.3 kDa
and isoelectric point of pH 5.7. The tuftelin gene contains 13 exons and alternatively
spliced mRNAs have been detected (Mao et al. 2001). An intact protein corresponding to
the cDNAs cloned as tuftelin, has not yet been isolated from the enamel matrix.
ENAMEL MINERALIZATION
The spaces defined by the Tomes' processes are initially filled with the ill-defined
mixture of matrix proteins and degradation products described above, but are richest in
the amelogenins (> 90%). Early electron microscopic studies of the nature of the enamel
matrix suggested that the matrix was organized into periodic substructures of globular
particles (Ronnhölm 1962; Travis and Glimcher 1964). That idea was challenged in many
studies over the years, but was finally substantiated when the amelogenin was sequenced,
cloned and the recombinant protein was prepared in sufficient quantity for study. In a
brilliant series of studies led by Alan Fincham (Fincham et al. 1994, 1995, 1998;
Moradian-Oldak et al. 1994, 1995, 1998a,b, 2000) it was shown that the amelogenins
showed a temperature-dependent, pH dependent self-association to form globular units
called “nanospheres” about 20 nm in diameter. The nanospheres aggregated to form an
extensive gel-like network, and it was proposed that, in the tooth the enamel apatite
crystals grow within this network to ultimately fill the entire space. The assembly of the
nanospheres, and their coalescence into larger fused aggregates depends on the integrity
of the amelogenin molecules. The most amino-terminal domain, the “A-domain,” appears
to be necessary for the assembly into uniform size nanospheres, while the “B-domain” at
the carboxyl-terminal region (lacking residues 157-173 in mouse recombinant
amelogenin rM179) blocked their fusion to larger, more irregular aggregates (Moradian-
Oldak et al. 2000). Deletion of the A-domain in transgenic mice delayed the initial
formation of aprismatic enamel in the molars and caused severe structural abnormalities
in the incisor enamel. B-domain deletion yielded a less drastic phenotype (Dunglas et al
2002). The amelogenins and most other proteins are degraded as mineralization proceeds
to make space for the hydroxyapatite. In the end, the proteins that do remain, principally
the enamelins, are accumulated at the surfaces of the apatite crystals. It is not clear as to
the function of the residual protein in the mechanical properties of the enamel, but it has
been suggested that they do moderate crack propagation and fracture in the otherwise
brittle, highly crystalline apatite.
Since it is removed, the function of the amelogenin rich matrix is not related directly
to the strength or toughness of the final product, in distinct contrast to the collagen of
bone. However, there must be a very specific role for the amelogenins in providing the
environment in which the crystals grow. In mouse molar teeth enamel mineral
organization is not uniform throughout the tooth but is distinctly less organized at the
region of the DEJ (Diekwisch et al. 1995). The enamel crystals begin as very thin ribbons
with elongated hexagonal cross sections representing the a,b planes. The crystals grow in
their c-axis direction. Figure 15 shows the earliest crystals forming in porcine enamel.
The organization of the ameloblast layer essentially determines the packing of the enamel
rods, probably via asymmetric secretion of matrix proteins through the adjacent Tomes'
processes. In different teeth, and in teeth from different species, the sizes and
organization of the enamel rods differ greatly. The materials properties of the different
enamels are determined by the layering and intertwining of the apatite rods. This process
