Tooth eruption
Eruption is a process of biological maturation, which comprises the axial
movement of a tooth from the developmental position within the jaw towards the
functional position in the occlusal plane. Eruption is a multifactorial process, whose
biological mechanism remains unknown. Among the various hypotheses that have been
proposed, the root growth and periodontal ligament theories are largely disregarded
today, because eruption also occurs in the absence of root formation and PDL. In more
recent studies the dental follicle theory has gained popularity.This organ is considered an
essential requisite for bone resorption in the eruption path as well as for the formation of
bone below the roots.
There is a predictable pattern to the eruption of teeth. With a few exceptions, tooth
eruption begins in the anterior and proceeds posteriorly, and mandibular teeth appear
before their maxillary counterparts.
More importantly there is a fairly predictable timing to the sequence of eruption. This has
had considerable significance for determining both the age at which children could be
employed in the 18th and 19th centuries, and unfortunately in our time, for forensic
medicine. While the timing of tooth eruption is predictable, the is considerable
variability. For example, the normal age of eruption for the primary central incisors is
usually given as 6 months of age, but it is perfectly normal for eruption to occur as early
as 3 months and as late as 12 months after birth. Dental age may be assessed clinically by
visually determining the number of teeth present, but a radiographic assessment of both
the stages of crown and root development, as well as the stages of eruption, is much more
reliable.
The exact mechanism behind tooth eruption and root genesis is unknown. Both the
enamel organ and dental follicle play a significant role in initiating and organizing the
eruption mechanism. If individual steps fail to synchronize, complications in eruption can
arise. In the some studies, cessation of eruption and root formation could be due to some
unknown aberration of the dental follicle or enamel organ. However, due to the multitude
of factors involved in tooth eruption, it is difficult to determine the exact cause of the
failure of eruption of some teeth.
Theories of tooth eruption
No one theory of how the forces might be generated to cause tooth movement has been
put forward that can account for all aspects of eruption. Nevertheless, available data
demonstrate that the mechanism of eruption is 1) a property of the periodontal ligament
or its developmental precursor, the dental follicle and 2) is probably multifactorial in that
more than one mechanism may be involved. The leading candidate theories include:
1. Root elongation
The major support for the theory of tooth movement involving root growth is that the
intraosseous phase of eruption does not begin until root formation has begun. In addition,
the root is only 2/3 formed at the time of emergence into the oral cavity. However,
rootless teeth do erupt and the length of the eruption pathway taken by some teeth is
longer than the root itself. This theory also requires that the bone at the base of the
alveolar crypt be more stable (resistant to pressure resorption) that the overlying bone or
primary tooth. However, once the eruption pathway has been formed, the resistance to
movement is presumably reduced and root growth may play a role.
2. Alveolar bone remodeling
The remodeling of alveolar bone (resorption 'above' and apposition 'below') has received
considerable attention. The cells of dental follicle and the reduced enamel epithelium
interact to recruit monocytes that differentiate into osteoclasts. These osteoclasts then
function to form the eruption pathway.
Several lines of evidence support this primary role of the dental follicle in tooth eruption.
First, artificial teeth will erupt if placed within a dental follicle. Second, damage to the
dental follicle will arrest eruption. Finally, experimental animals in which osteoclast
differentiation or function is defective exhibit delayed eruption. In contrast, little data is
available to demonstrate how the compensatory apposition of bone at the base of the
crypt may be regulated. For permanent anterioir teeth, the role of the dental follicle may
be to simply widen a pre-existing eruption pathway. Unlike all the primary teeth and all
the other permanent teeth, the developing toothbuds for the incisors maintain their
connection to the oral mucosa via a band of connective tissue (gubernacular cord) that
connects of the dental follicle and the lamina propria via the gubernacular canal.
3. Periodontal ligament formation and renewal
The third major theory of tooth eruption involves the periodontal ligament, and two
separate mechanisms have been proposed. The first is dependent on the constant turnover
(remodeling) of collagen fibers in the ligament. During maturation, collagen fibers
'shrink' in length by about 10%. Because of the orientation of these oblique collagen
fibers, the vector of force generated in aggregate is directed occlusally.
The second mechanism involves a small, but measurable, contractile force that can be
generated by fibroblasts. Fibroblasts are the most numerous cell type in the periodontal
ligament, and they can "attach" to collagen type I fibers via fibronectin and integrins. The
difficulty with the periodontal ligament theory is that the periodontal ligament does not
become highly organized until after the tooth begins to come into functional occlusion.
Therefore, the periodontal ligament theory is unlikely to explain either the intraosseous or
mucosal phases of eruption.
4. Periodontal ligament hydrostatic pressure
One final theory of tooth eruption has been proposed, which involves periodontal/tissue
vascular pressure. This theory requires that eruptive movements are maintained by
pressure differentials along the periodontal ligament space, and that periodontal tissue
pressures are high. Support for this mechanism includes 1) the predictable effects of
vasoactive drugs on eruption behavior, 2) the distribution of fenestrations in alveolar
bone proper (greater number at the base) and 3) changes in the number of fenestrations
during different phases of eruption.
Molecular regulation
Relatively little is known about the molecular regulation of tooth renewal, i.e. shedding
of the deciduous teeth and development and eruption of the secondary teeth. There
appears to exist a regulatory relationship between the development of the primary teeth
and the successor , and it may be possible that both activating and inhibitory effects are
involved.
The localization of DF-95 to reduced enamel epithelium (REE) provides biochemical
evidence of the REE involvement and initiation of eruption. The activation of proteases
in the enamel organ after crown formation is thought to cause DF-95 fragmentation and
release of metalloproteinases by the dental follicle to initiate eruption. Growth factors
such as TGF-B, EGF, Interleukin-alpha-1, and CSF-1 have been demonstrated to act as
molecular regulators of eruption. The timing of the cascade of biochemical processes that
trigger the initiation of root genesis in congruence with the rate of eruption is not known.
Molecular studies have revealed that the instructive and permissive tissue interactions
during mouse tooth development are mainly mediated by growth factor signaling .
Development from initiation to eruption is governed by a sequential and reciprocal
signaling process rather than simple one-way messages. The signaling involves all major
signaling pathways, including TGF, FGF, Shh and Wnt as well as Eda, Notch, and EGF
signaling, and studies with mouse mutants have shown that they are needed
simultaneously during critical stages of development. Expression of signals is often
redundant: several FGFs are expressed in the initiation stage epithelium, in the enamel
knot and in the dental mesenchyme and they signal to receptors expressed differentially
by mesenchymal and epithelial cells . Similar co-expressions are evident for BMP and
Wnt signals.
Nerve growth factor (NGF) is an important neurotrophin (NT) for the development,
differentiation, function, and survival of neurons. Based on detection of receptors for
NGF it has been proposed that NGF also has an effect on many non-neural tissues.
Different receptors for NGF have been identified in recent year. Nerve growth factor
receptor (NGFR) expression has been investigated in relation to the developing tooth
bud. the locations of NGF and NGFR have been described in primary tooth buds for
different developmental stages in rodents , and in sections of pre-natal human tooth buds.
Intraosseous tooth eruption is not possible without formation of an eruption path. The fact
that bone resorption and bone formation are polarized around erupting teeth and that
these events depend upon the adjacent part of the dental follicle strongly indicate that
tooth eruption is regulated by the dental follicle. The relationship between NGFR
expression in the dental follicle and tooth eruption is unknown.
Tooth eruption is a precisely timed, complex process, which requires localized bone
resorption to form an eruption pathway and a functioning dental follicle to regulate local
bone metabolism . Colony-stimulating factor (CSF)-1 is considered to play a role in the
complex process of tooth eruption. It has been proposed that CSF-1 enhances local
alveolar bone resorption by increasing the number of mononuclear cells in the dental
follicle and osteoclasts on adjacent alveolar bone surfaces. Dental follicle cells transcribe
and translate CSF-1 and express receptors for CSF-1. The peak gene expression of CSF-1
in the follicle of the rat lower first molar, is at day 3 postnatally, coincidental with the
timing for the maximum influx of monocytes into the follicle The toothless (tl/tl) rat is
an osteopetrotic animal in which osteoclast, macrophage, and mononuclear cell numbers
are reduced. In this osteopetrotic animal, teeth form but fail to erupt, and remain
embedded within their bony crypts. The bone defect in this mutation is not cured by bone
marrow transplantation but is improved following treatment with CSF-1. CSF-1 affects
the proliferation, differentiation, and survival of mononuclear phagocyte lineage cells and
promotes the formation of osteoclasts from hematopoietic stem cells. Treatment of tl/tl
mutants with CSF-1 increases osteoclasts, macrophages, and bone resorption and permits
tooth eruption.
Cellular regulation
Osteoclasts form through the differentiation of the hematopoietic precursors in the
colony-forming
unit
granulocyte/macrophages
line
(CFU-GM).
These
monocytemacrophage precursors are present in bone marrow as well as in circulating
blood. Mature and active osteoclasts can be found on the endosteal surfaces in Haversian
canals and on the periosteal surface beneath the periosteum, but are rarely found at other
locations within bone. The receptor activator of nuclear factor-kappa ligand (RANKL) is
now thought to be the primary molecule responsible for differentiation and function of
osteoclasts.This ligand, associated with the Tumor Necrosis Factor (TNF) family, is
expressed on the plasma membranes of immature osteoblasts as well as on the surface of
stromal cells in soluble and secreted forms. Binding with its receptor, receptor activator
of nuclear factor (RANK), leads to preosteoclast differentiation and stimulates their bone
resoptive capacity. Osteoprotegrin (OPG), also a member of the TNF family, is a decoy
receptor of RANKL and is also produced by osteoblastic cells. OPG competes for the
binding of RANKL, and limits the docking of the RANKL with RANK, decreasing the
initiation of preosteoclast differentiation and activation.
The OPG/RANKL/RANK system has been recognized as the final mediator of
osteoclastogenesis and the control mechanism for bone turnover. The OPG to RANKL
ratio is often used to indicate if a particular sample is in the resorption or deposition
phase. Numerous hormones, cytokines, molecules, and biologic conditions affect the
expression of the members of the OPG/RANKL/RANK system. One central component
in osteoclast regulation is Tumor Necrosis Factor α (TNF- α). Many of the other factors
involved in osteoclastogenesis either increase or decrease TNF-α itself, its receptor, or
the induction factor, Nuclear Factor Kappa Beta (NF-kβ). TNF- α and Interluekin 1βeta
(IL-1β) have been found to decrease OPG availability to bind RANK through the
production of osteoprotegrin ligand. The secondary effect is increased RANK/RANKL
binding and subsequent osteoclasts differentiation and activation. Parathyroid hormone
(PTH), Vitamin D3, Protein Kinase C (PKC), Protein Kinase A (PKA), Prostaglandin-2
(PGE-2), low oxygen tension, and nitric oxide accumulation all lead to the stimulation of
resident stem cells and uni-nucleated preosteoclasts via the upregulation of RANK and
RANKL.
The biochemical processes involved in the control of tooth eruption are well known.
During eruption, cells, proteins and enzymes change in the dental follicle and several
growth factors and proteins accelerate or retard eruption rate.
Genetic regulation
The relationship between rate of tooth eruption and variation in life-history traits and
environmental factors in mammals is not well understood. In addition to size, it is
expected that eruption is delayed:
(1) by generally low body condition,
(2) orin areas with mineral deficiencies.
(1) Low body condition (i.e. a residual effect of weight after controlling for height;
delayed eruption
of permanent teeth in humans. However, the effect of body condition was not large and it
is assumed that most of the variation in human dentition is explained by genetic variance
among populations. In ungulates, only two studies have investigated the relationship
between tooth development and somatic growth, but neither of them have separated the
effects of body size and body weight. found that the number of erupted incisors increased
with body weight in mule deer this provide graphical evidence that individual fallow deer
Dama dama with shortmandible and lowbodyweight erupt their first molar later than
larger conspecifics. No studies of ungulates have investigated variation among different
populations.
(2) Calcium, in addition to phosphorus, is a limiting element in the formation of bone
(Bazely, 1989) and teeth. Calcium deficiency in forage was found to cause dental disease
in pet rabbits Oryctolagus cuniculus .Tooth eruption was delayed in six weaning sheep
Ovis aries fed on cereal roughages poor in calcium, compared to five sheep where ground
limestone was added to the diet. No study has explored whether calcium is limiting for
tooth development in natural populations of mammals.
A study gives report on how variation in the tooth eruption of 2241 yearling red deer
Cervus elaphus was related to phenotypic ( jawbone size, body weight and body
condition) and environmental variables (bedrock calcium, local density and distance from
the coast). The prediction that eruption is earlier in larger and fatter deer was tested. The
density of local deer and their distance from the coast are known to correlate,
respectively, negatively and positively with red deer body weight .
Later eruption of permanent teeth with increasing deer density, and earlier eruption with
increasing distance from the coast was therefore expected, but no residual effect after
body weight was also entered in the model if the effect of density and distance from the
coast operated only through body weight. Lastly, earlier eruption in areas with calcium
rich bedrock was predicted.
Cellular,Molecular and Genetic determination of
Tooth Eruption
Prepeared by
Bushra Habeeb Ahmad