Orthodontic tooth movement occurs through the application of mechanical forces that cause the alveolar bone and periodontal ligament to bend or flex. This movement is regulated by various cellular and molecular mechanisms. There are two main theories that describe how orthodontic forces are converted into biological responses: the pressure-tension theory and bioelectric theory. The pressure-tension theory proposes that orthodontic forces alter blood flow in the periodontal ligament, resulting in the formation and release of chemical messengers that stimulate cellular activity and bone remodeling. The bioelectric theory suggests that bending of the alveolar bone generates piezoelectric signals that act as cellular signals to initiate tooth movement. Understanding these biological mechanisms of tooth movement could help

1. _____________________________________________________________________________________________________
*Corresponding author: E-mail: amolp66@yahoo.com, amolp66@gmail.com;
British Journal of Medicine & Medical Research
16(12): 1-10, 2016, Article no.BJMMR.27019
ISSN: 2231-0614, NLM ID: 101570965
SCIENCEDOMAIN international
www.sciencedomain.org
Biology of Tooth Movement
Anand Sabane1
, Amol Patil1*
, Vinit Swami1
and Preethi Nagarajan1
1
Department of Orthodontics, Bharati Vidyapeeth Deemed University, Pune, Maharashtra, India.
Authors’ contributions
This work was carried out in collaboration between all authors. Authors AS, VS and PN collected the
articles, designed the review and wrote the article. Author AP corrected and rearranged the article and
the entire review. All authors read and approved the final manuscript.
Article Information
DOI: 10.9734/BJMMR/2016/27019
Editor(s):
(1) Joao Paulo Steffens, Department of Stomatology, Universidade Federal do Parana, Brazil.
(2) Karl Kingsley, Biomedical Sciences and Director of Student Research University of Nevada,
Las Vegas - School of Dental Medicine, USA.
(3) Salomone Di Saverio, Emergency Surgery Unit, Department of General and Transplant Surgery,
S. Orsola Malpighi University Hospital, Bologna, Italy.
Reviewers:
(1) Ashetty Nj, Manipal College of Dental Sciences, Manipal University, Mangalore, India.
(2) D. S. Pushparani, Srm University, India.
(3) A. Bhagyalakshmi, JSS University, India.
(4) Fernando Lima Martinelli, Pontifical Catholic University of Rio Grande do Sul, Brazil.
Complete Peer review History: http://sciencedomain.org/review-history/15417
Received 16
th
May 2016
Accepted 27th
June 2016
Published 17
th
July 2016
ABSTRACT
Research in the field of cellular and molecular biology is relatively lagging in comparison to
mechanical advances in the field of orthodontics. Even though the mechanical advances are used
quite carefully during orthodontic tooth movement, traumatic effects on the periodontium have not
been totally prevented. This may be because of a lack of complete understanding of the cellular
complexities. Proper understanding of cellular and molecular biology will help design mechanics
that will produce maximum benefits during tooth movement with minimal tissue damage. The rate of
tooth movement depends on the rate at which bone remodels and hence, better knowledge of
specific biochemical pathways in individual patients will provide a key to predicting how well teeth
respond to mechanical forces. This in turn will provide for better tooth movement and faster
treatment procedures.
The pressure tension theory as well as the bioelectric theory have been discussed in detail along
with various chemical mediators with the lipo-oxygensase pathway as well as they cyclooxygenase
pathway. Role of neurotransmitters and vasoactive amines along with mechano-transduction has
been discussed in the review. These predictors, however, need further work to validate reliability.
Review Article

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Keywords: Biology; tooth movement; pressure tension theory; mechanotransduction.
1. INTRODUCTION
The movement of a tooth occurs due to the
translocation of the tooth from one position in the
jaw to another. Extrinsic forces applied to the
crown of the tooth during physiological,
therapeutic or pathological processes cause
tooth movement [1]. Teeth can be repositioned
and retained in a new position in the jaw using
orthodontic appliances, through the intervention
of the cells of the periodontium. Research in the
field of cellular and molecular biology is relatively
lagging in comparison to mechanical advances in
the field of orthodontics. Even though the
mechanical advances are used quite carefully
during orthodontic tooth movement, traumatic
effects on the periodontium have not been totally
prevented. This may be because of a lack of
complete understanding of the cellular
complexities.
Proper understanding of cellular and molecular
biology will help design mechanics that will
produce maximum benefits during tooth
movement with minimal tissue damage. The rate
of tooth movement depends on the rate at which
bone remodels and hence, better knowledge of
specific biochemical pathways in individual
patients will provide a key to predicting how well
teeth respond to mechanical forces. This in turn
will provide for better tooth movement and faster
treatment procedures. A thorough knowledge of
the biochemical mediators of orthodontic tooth
movement and their mechanisms will provide a
rational for better and effective treatment [1-4].
Therefore an effort is made through this review
titled “Biology of tooth movement” to provide an
opportunity for the reader to understand and
update the knowledge on the latest research on
biological changes occurring at the molecular
and genetic level [5-7]. This would in turn help an
orthodontist in delivering better mechanics,
producing quicker tooth movement with minimum
tissue damage and maximum comfort to the
patient.
2. THEORIES OF TOOTH MOVEMENT
Alveolar bone resorption and deposition during
orthodontic tooth movement is a cell – mediated
process regulated by various factors. However
the mechanisms involved in conversion of OF
(Orthodontic Force) into biologic activity are not
completely understood.
There are two possible control elements that
form two major theories of orthodontic tooth
movement. They are:
1) Biological Electricity.
2) Pressure – Tension in the periodontal
ligament (PDL).
2.1 The Bio – Electric Theory
This theory explains that the electric signals that
are produced when alveolar bone bends or
flexes, are at least partly responsible for tooth
movement. Electric signals that might initiate
tooth movement initially were thought to be
Piezoelectric.
Piezoelectric signals have two unusual
characteristics [8]:
1. A quick decay rate – when force is applied,
a piezoelectric signal is created, that
quickly dies away to zero even though the
force is maintained.
2. The production of an equivalent signal
opposite in direction when force released.
Ions in the living bone interact with the electric
field generated when the bone bends, causing
temperature changes as well as electric signals.
The small voltage that is observed is called the
“streaming potential” These voltages, though
different from piezoelectric signals in dry
materials have in common their rapid onset and
alterations, Streaming potential could be
generated by the application of external electric
fields. Sustained force of the type used to induce
orthodontic tooth movement does not produce
prominent stress generated signals. A second
type of electric signal can be observed in bone
that is not being stressed, which is called the
“bioelectric potential”. Metabolically active bone
produces electro negative changes that are
generally proportional to their activity. Cellular
activity can be modified by adding exogenous
electric signals, which affect cell membrane
receptors, membrane permeability or both.
Baumrind and Grimm demonstrated that alveolar
bone deflection is routinely produced by
orthodontic force (O.F). and these forces are
accompanied by consequential changes in the
periodontal ligament [9]. On the other hand,
Hellar and Nanda tested the role played by

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periodontal fibers in transmitting stress
generated by orthodontic forces to bone. Epker
and Frost [10] documented changes in the
curvature of bone surfaces, caused by loading
and correlated these changes with specific
cellular response [11]. Zengo and associates
investigated the nature of electro-chemical
relationship associated with the dentoalveolar
complex using simulated OF. Both in-vivo studies
indicated that areas that are electro-negative
were characterized by elevated osteoblastic,
activity and areas of electropositivity were
characterized by elevated osteoclastic activity
[12].
Davidovitch and associates were able to show
that accelerated Orthodontic tooth movement
resulted when exogenous electric current was
administrated in conjunction with orthodontic
forces, which further increased cellular response
to electrical stimulation [13,14]. This suggests
that the piezoelectric response propagated
by bone bending incident to of application
may be functioning as “Cellular first
messenger.”
2.2 The Pressure Tension Theory
This theory explains the cellular changes
produced by chemical messengers during tooth
movement. This is mainly because of alteration
in blood flow through the PDL. The alteration in
blood flow quickly creates changes in the
environment. For example, oxygen levels would
fall in the compressed area but might increase on
the tension side and the relative proportions of
other metabolites would also change in a matter
of minutes. Orhan Tuncay and Daphane
observed that low oxygen tension causes
increased cellular proliferation and decreased
Adenosine triphosphate (ATP) activity and partial
pressure of oxygen (Po2) while hypoxic
conditions result in suppressed cellular
proliferation and increased ATP activity [15].
These chemical changes acting directly or by
stimulating the release of other biologically
active agents then would stimulate cellular
differentiation and activity.
In essence, this view of tooth movement shows
three stages.
a) Alteration in blood flow in the PDL.
b) The formation and / or release of Chemical
Messengers.
c) Cell response.
2.2.1 Messenger systems
The cells in each system have the ability to
produce a large number of chemical agents
possessing stimulatory effects or inhibitory
effects on other neighboring cells through the
synthesis and release of potent substances that
modulate cellular behavior. “The Primary
Stimulus” or “First Messengers” may alter all
activity through the plasma membrane. The
responsive cells possess receptors for these
substances. Their interactions lead to a transient
increase in the intracellular level of “Second
Messengers” followed by enzymatic
phosphorylation, protein synthesis, cellular
events that regulate cyclic adenosine mono
phosphate (cAMP) production (Second
Messenger) and cell response (Chart 1). The
agonists, primary stimulus or first messenger
such as hormones or mechanical forces
(Orthodontic Force) may alter activity through the
plasma membrane. The production of second
messenger (cAMP) pathway is regulated by
stimulatory (Rs) or inhibitory (Ri) receptors.
Chart 1. Release of cycli AMP (Secondary
messenger)
The intra-membranous components that have
been shown to mediate effects of the extra
cellular stimuli are calcium ions and cell
membrane enzymes. This interaction between
receptors and their respective proteins i.e
stimulatory and inhibitory G proteins (Gs & Gi)
stimulate or inhibit Adenylate cyclase. This
enzyme helps in the formation of cAMP from
ATP. The agents such as Forskolin can activate
adenylate cyclase directly. cAMP is known to
activate protein Kinase – A, an enzyme
responsible for protein phosporylation which

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causes cell response. Hydrolysis of cAMP into 5
AMP is affected by Phosphodiesterase enzyme
(PDE) The concentration of cAMP is maintained
by preventing the hydrolysis to 5 AMP in the
presence of PDE inhibitors. In support of the
second messenger pathway involvement in
Orthodontic tooth movement, Davidovitch5
and
Shanfield reported that cAMP concentrations
were significantly higher in alveolar bone extract
taken from orthodontically treated cats as
opposed to untreated alveolar bone sample.
2.2.2 Phosphate Inositol (PI) pathway
A further “Second Messenger” system was
investigated in 1950’s by Hokin and Hokin who
showed an increase in Phosphate incorporation
into cell membrane phospholipids in response to
many stimuli. However, the importance of
phospholipids as a messenger system was not
fully appreciated until 1980’s when Streb and
others demonstrated that, products of Inositol-
Lipid breakdown could cause release of
intracellular calcium ions. Membrane events that
result in the reduction of Inositol phosphates are
similar to those for generation of cAMP. In this
pathway, agonist binds cell surface receptors
followed by receptor-G-protein interaction,
resulting in the formation of Inositol phosphate.
Inositol phosphate in the presence of
phospholipids gets converted to
phosphotidylinositol biphosphate (Chart 2).
Chart 2. Inositol pathway
The Phosphodiesterase then cleaves IP2 into
diacylglycerol (DG) and Inositol Triphosphate
with the subsequent release of calcium from
intracellular stores. Intracellular calcium ions are
mobilized from the endoplasmic reticulum.
Calcium thus released is responsible for protein
phosporylation, which leads to early and
sustained cell response. IP3 in turn is either
dephosphorylated to free Inositol, which is then
recycled into the poshosphatidyl inositol (P.I.)
Pathway or phosphorylated to form Tetra Inositol
Phosphate. This IP4 may have a role in gating
calcium through calcium channels of the
membrane. IP4 is a proven mediator of
mitogenesis in a variety of cell types. In addition
to the production of Ip3, DG is formed, which
remains within the plane of the cell membrane
and activities protein kinase-C (PKC). Protein
kinase-C is an enzyme responsible for protein
phosphorylation which leads to cell response.
Phospholipids from diacylglycerol in the
presence of phospholipids also give rise to
Arachidonic acid (Eicosanids). With these
developments it became clear that second
messengers other than cAMP, such as
phospholipid metabolites, i.e. Inositol Phosphate
and Diacylglycerol could mediate the effects of
mechanical deformation.
2.2.3 Prostaglandins and tooth movement
Prostaglandins were first discovered by Von
Euler [16] in 1934. The compound was isolated
from human semen and it was believed at that
time that the prostate gland was major source. It
is now known that prostaglandins are produced
by nearly all tissues, but the name has been
retained. The ability to stimulate or inhibit tooth
movement by addition of exogenous PGE
or Indomethacin respectively suggests that
mechanical forces are mediated by prostaglandin
production. Based largely on this, Yamasaki [17]
and co-workers demonstrated that injection of
Prostaglandins increased Osteoclast numbers.
Cycloxygenase inhibitors such as Indomethacin
and other Non steroidal anti-inflammatory drugs
(NSAIDs,) which inhibit prostaglandin synthesis,
inhibit the appearance of osteoclasts. Further
work by Yamasaki showed that local
prostaglandin injection could also increase the
rate of orthodontic tooth movement in primates.
An Animal experiment conducted by Bhalaji [18]
(On rabbits) also showed that administration of
prostaglandin increased the rate of tooth
movement.
2.2.4 Arachidonic acid pathway
An earlier report in a rabbit model found only a
significant decrease in osteoclast number and
not in the degree of tooth movement. Sandy

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[19,20] and Harris suggested that prostaglandins
alone do not account for bone remodeling
associated with tooth movement.
Leukotrienes and Hydroxy Eicosa Tetra-enoic
acid (HETE’s) produced from the same substrate
(Arachidonic acid) could account for this
discrepancy. It has been demonstrated that
these inflammatory modulators potentially resorb
bone. Leukotrienes, which are also metabolites
of Arachidonic acid, were originally demonstrated
in leukocytes and were called leukotrienes. It is
possible then, since prostaglandins are not fully
responsible for bone remodeling associated with
tooth movement, lipoxygenase products may
also be involved. A rat orthodontic model has
been used to demonstrate that inhibition of
leukotriene synthesis can significantly reduce
orthodontic tooth movement. Both prostaglandins
and leukotrienes have a common parent
substrate (Arachidonic acid), which is released
from the phospholipids of the cell membrane
by the action of phospholipase enzyme.
(Phospholipids are produced by diacylglycerol).
However, factors controlling these events may
both be mediated by intracellular alterations in
the cyclic nucleotides. The following sequence of
events is considered. First, activation of the
enzyme phospholipase with subsequent release
of Arachidonic acid results in increased cAMP
production. Second, there is also an increase in
intracellular calcium and stimulation of DNA
Synthesis. Arachidonic acid is metabolized by
cyclo-oxygenase enzymes producing PG and
Thromboxanes. Metabolism through lipo-
oxygenase pathway results in production of
leukotrienes and HETE’s (Hydroxy Eicosa
Tetraenoic acid) (Chart 3).
Chart 3. Arachidonic pathway
To sum up the event, as shown by Mostafa et al.
[21], it is possible that there are two biologic
pathways generated by orthodontic forces (Chart
4):
Pathway – I: Represents a more physiologic
response that may be associated with normal
growth and remodeling.
Pathway – II: Represents the production of a
tissue inflammatory response generated by the
Orthodontic Force.
Chart 4. Biologic pathways generated by
orthodontic forces
Pathway – I: From the Pathway – I It can be
explained that Orthodontic Force creates
pressure and tension ultimately leading to bone
bending. Since collagen fibers possess
piezoelectric properties, the primary response to
orthodontic force is the generation of tissue
bioelectric polarization in response to bone
bending. Alternatively, it has recently been
demonstrated by Somjen et al. that bone cells
maintained in culture release prostaglandins in
response to pressure. It is not clear whether
piezoelectric effects themselves stimulate the
observed prostaglandin synthesis or whether
alternative independent events are involved.
However, there is circumstantial evidence that
electrical stimulation elicits prostaglandin
synthesis. It is clear from the literature that both
prostaglandin synthesis and membrane electrical
polarization, by the piezoelectric process act on
the cell surface cyclic nucleotide pathway,
generating changes in the levels of cAMP. So
far, the events described do not take into

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consideration the directional control of tooth
movement. It has been demonstrated that during
bone bending, areas of convexity assume a
positive charge and areas of concavity assume
negative change.
Interestingly, it has also been shown that
electrically neutral or positive areas promote
osteoclast activity and zones of electro negativity
support osteoblastic activity. This may explain
how matrix change polarization contributes to the
directional control of orthodontic bone
remodeling. In addition, the charged matrix may
activate membrane polarization in turn effecting
cAMP levels. It has been recently suggested by
Rodman and Martin that bone formation and
resorption are synchronized by a diffusible
product produced by the osteoblast and named it
a “Coupling Factor”. The presence of such a
coupling factor would indicate that perhaps the
osteoblast responds to the initial environmental
condition and subsequently regulates
osteoclastic activity. This would provide for a
mechanism in which net bone formation equals
net bone resorption. The coupling factor could
then explain the observation that, both bone
resorption and formation occurs in areas of
pressure and tension, and in the opposite
direction thus maintaining the alveolar bone plate
thickness.
Pathway – II: In pathway – II the tissue injury
generated by OF elicits a classic inflammatory
response. Inflammatory processes are triggered
along with the classic vascular and cellular
infiltration. Lymphocytes, monocytes and
macrophages invade the inflamed tissue and in
all likelihood contribute to prostaglandin release
and hydrolytic enzyme secretion. It has been well
documented that local inflammatory responses
stimulate osteoclastic activity. This increase in
osteoclastic activity is believed to be generated
by local elevation of prostaglandin and
subsequent increase in cellular cAMP.
The strongest evidence for the presence of a
chemical mediator released in response to the
inflammatory reaction is the fact that bone
remodeling persists for several days after
cessation of OF. The inflammatory response is
also characterized, by hydrolytic enzyme
secretion. This has important relevance to
connective tissue turnover. It is believed that
collagenase exists in an inactive form and may
be activated plasminogen activator, which digest
the osteoid, exposing the mineralized matrix and
allowing the osteoclast to act. This has been
brought about by the hydrolytic enzyme
produced by the lymphocytes, monocytes and
macrocytes.
3. ROLE OF NEUROTRANSMITTERS IN
ORTHODONTIC TOOTH MOVEMENT
Another outcome of the physical distortion by
forces on the para dental tissues is its effect on
peripheral nerve fibers and terminals.
Neuropeptides stored in nerve terminals within
the PDL either may be released into the
extracellular space as the applied stress persists
or stream towards the ganglion (Chart 5).
Chart 5. Role of neurotransmitters in
orthodontic tooth movement
Neuropeptides are distributed widely in many
tissues, some of the neuro peptides particularly
Substance P (SP), Vasoactive intestinal
polypeptide (VIP) and calcitonin gene related
peptides (CGRP) have been shown to affect
bone cells directly or through their effects on the
vascular system by increasing the permeability.
Substance P [22] has been identified in dental
tissues around the blood vessels in the dental
pulp. They are responsible for vasodilatation and
extravasation of plasma and migration of
leukocytes into extra vascular tissues. When
Substance P was incubated for 48 hours with
cultured human synoviocytes of arthritic patients,
it caused significant elevation of prostaglandin-E
(PGE) and collagenase release into the medium
as well as increase in cell proliferation.
Vasoactive intestinal polypeptide was first
isolated from hog intestinal tissue. It is a potent

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vasodilator shown to stimulate bone resorption in
vitro through a cAMP related mechanism. VIP in
the cat dental pulp has been reported.
4. SHAPE CHANGE IN CELLS
4.1 Mechanism for the Transduction of
Mechanical Forces
The development of techniques to isolate and
culture cell types and methods of deforming cell
layers or altering cell shape have suggested that
a definite relationship exists between cell shape
and metabolic activity. Folkman and Mascona
showed that flattened cells synthesize more DNA
than rounded cells. Aggler and Frich produced
evidence that catabolic rather than anabolic
events are associated with rounded cells.
Prostaglandins and parathyroid hormone (PTH)
induced shape change in bone cell culture. It is
conceivable then that in pressure sites, cells are
rounded and have catabolic effects and in
tension sites cells are flattened and are therefore
in an anabolic or in a synthetic mode. It is
important to realize that shape change by
cultured cells in vitro in response to various
hormones and growth factors may not
necessarily occur in vivo.
4.2 Cytoskeleton Matrix Interactions
Several researchers have shown that shape
changes in cells could be brought about by non –
chemical means and this was mainly because of
the reorganization of the cytoskeletal protein.
The three main components of the cytoskeleton
are i) Microtubules, ii) Microfilaments and
iii) Intermediate filaments Microfilaments are
perhaps the best situated of the three systems to
detect these changes. The major subunit protein
of the microfilaments is Actin. There are,
however, many associated proteins such as
myosin, Tropomyosin, Vinculin, and Talin.
Microfilament bundles terminate at specialized
Talin sites of the cell membrane forming a
junctional complex with the extracellular matrix.
These tight adhesions are known as Focal
Contacts or Adhesion Plaques. The cell
membrane integral proteins termed Integrins
span the cell membrane from the cytoplasm to
the extracellular matrix. Integrins do not bind
directly to microfilaments such as ACTIN, but are
dependent on associated proteins for this
function (e.g. Fibronectin extracellularly and Talin
intracellularly). Actin Vinculin bind to this Talin –
Integrin complex.
It is possible therefore to visualize a complex set
of events that might arise either from distorting a
cell, cell membrane, or extracellular matrix
mechanically or by inducing a change in cell
shape with hormones and growth factors. To
date there is little published work regarding
changes in the cytoskeleton with mechanical
forces, but Banes et al found decrease in Tubulin
and suggested that this may have a role in
mediation of mechanical stress. After discussing
the basic biochemical reaction to O.F. let us
go into the queries put in the beginning of the
talk.
5. HOW DO CELLS DISTINGUISH
BETWEEN TENSION AND PRESSURE
(COMPRESSION)?
If bone cells cannot distinguish between tensile
and a compressive mechanical stress, how can
bone resorption takes place on the compression
side of the alveolar bone during orthodontic tooth
movement. At the “Biology of Tooth Movement”
conference held at Farmington in Nov. 1986 it
was suggested that the answer was likely to be
found in the field of cytokine biology. According
to this hypothesis, formation or resorption of
bone depends on i) the cytokines produced
locally by mechanically activated cells and ii) the
functional state of the available target cells. As
we know, cells communicate among themselves
as well as with other cells through the synthesis
and release of potent substances that modulates
cellular behavior. The responsive cells possess
receptors for these substances and their
interaction leads to a transient increase in the
intracellular level of “Second Messengers”
followed by enzymatic phosporylation and protein
synthesis.
5.1 Cytokines as Mediators of
Mechanically Induced Bone
Remodeling
Cytokines [8] are short – range soluble mediators
released from cells, which modulate the activity,
of other cells. The first ones identified were
lymphokines produced by lymphocytes. Then it
was thought that lymphocytes were the only cells
that could produce such factors, and hence they
named them as “lymphokines”. It is now known
that many different cell types can produce these
agents and the term cytokines is used.
Inflammatory cells produce numerous cytokines,
which mediate various stages of inflammation.
Well over 50 cytokines have been described till

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date. Some of these cytokines particularly
Interleukin – 1 alpha, and 1 beta, Tumor
Necrosis Factor, Gamma Interferon have been
implicated in the mediation of bone remodeling
process in vitro.
Interleukin – 1 originally was defined as a
monocyte / macrophage product with numerous
biological functions such as bone resorption, and
fibroblast proliferation. Interleukin – 1 promotes
release of collagenase and patients with chronic
gingivitis. It was also detected in the periodontal
tissues of cat canine teeth after the application of
a tipping force, which provided the first
experimental evidence to support the hypothesis.
5.2 Cytokines and Interaction between
Osteoblast and Osteoclast: How do
Cytokines Mediate Mechanically
Induced bone Remodeling?
It has been realized that osteoblasts have the
receptors for PGs, PTH and Vit D, but not
osteoclasts. The transmission of signals from
osteoblasts to osteoclasts occurs in two ways.
Osteoblasts respond to systemic and local
agents by producing collagenase. Osteoclasts
cannot / do not resorb bone unless the surface
osteoid layer is removed. Therefore osteoblasts
might facilitate bone resorption through mineral
exposure. The osteoblasts, having recognized
the resorptive signal somehow transmit it to the
osteoclasts. Rodman and Martin hypothesized
that bone resorbing agents such as PTH may
induce a change in shape of the osteoblasts
which would facilitate the access of osteoclasts
to bone surface. Thus a low concentration of
PTH promotes bone formation, but at high
concentration will facilitate bone resorption.
Resting bone surfaces are covered by a thin
layer of non – mineralized osteoid, which
protects the underlying mineralized bone from
uncontrolled osteoclastic action. This is
supported by observations on resting bone,
where osteoblasts lie flat on the bone surface.
When PTH stimulates these cells they change
shape, becoming more round and thus exposing
the underlying minerals. There is now good
evidence that removal of this osteoid is brought
about by collage production by the osteoblasts.
This indicates that bone resorption occurs as a
tightly defined event with the osteoblasts
controlling the critical phase. This mechanism is
unlikely to be the major regulatory factor because
it can only influence the activity of already
differentiated osteoclasts.
Resorptive signals may be transmitted to
osteoclasts by the cytokines, which are produced
by the osteoblasts. The cytokines may either
activate osteoclast directly or promote their
recruitment and differentiation from their
precursor cells. Thus osteoblasts are no longer
regarded simply as bone forming cells. Whether
all osteoblasts are capable of presenting
resorptive signals to osteoclasts or their
precursor cells is not clear. It is possible that a
population of ‘Helper’ osteoblasts exists in bone
distinct from those involved in matrix synthesis,
whose principle function is to regulate resorption.
Alternatively, all osteoblasts may have the
potential to act as helper cells act some stage in
their life cycle. Once osteoid formation has
ceased, the surface resting osteoblasts acquire
the ability to respond to resorptive signals.
An additional theory has been put forward that in
response to PTH, osteoblasts secrete a soluble
activator for osteoclasts known as Osteoclast
Activating Factor (OAF). Now it is clear that
although osteoclast is the principle bone –
resorbing cell, the osteoblast is now recognized
as the cell, which controls both formative and
resorptive phase of the bone remodeling cycle.
Therefore whether bone formation or resorption
predominates at a particular site is determined by
the cytokines produced locally by mechanically
activated cells as well as the functional state of
the available target cells. According to Sandy &
Meghji [15,16], in addition to the various above
mentioned mechanisms by which osteoclastic
bone resorption is stimulated, osteoblasts are
also involved in signal transmission in response
to binding of hormones like PGE2 or
parathormone to a receptor on the osteoblast.
Osteoblasts produce a soluble mediator for
activation and recruitment of osteoclasts.
Also, they produce matrix metalloproteinase
(MMP’s) for breakdown of nonmineralised
osteoid layer. Osteoclasts can then remove bone
after the surface, osteoid layer is removed by the
MMP’s and mineralized matrix is exposed.
Osteocytes i.e. osteoblasts trapped in the
trapped in the mineralized bone matrix are also
thought to play a role as mechanical sensors
detecting mechanical loading of bone which
results in cellular response. Matrix
metalloproteinases [23] are extracellular matrix
degrading metallo enzymes collectively known as
MMP's. Endogenous inhibitors exist for these
metallo enzymes & are known as tissue inhibitors
of metalloproteinase (TIMP's). These metallo

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enzymes are called metallo, because they
depend on Zn++ and Ca++ for their activity. They
act at neutral pH and digest the major macro
molecules of connective tissues. Tissue
breakdown occurs where MMP's are in excess of
TIMP's. The significance of these enzymes in
orthodontic tooth movement is that the MMP's
and TIMP's are both increased during
mechanical deformation of sutures.
The Osteoclast apart from its osteolytic function
also plays an important role in the development
and growth of bone by releasing polypeptide
growth factors from the extracellular mineralized
matrix [24-26]. These factors are generally
referred to as Bone Derived Growth Factors
(BDGF) and are known to include Bone
Morphogenetic Proteins (BMP) Platelet Derived
Growth Factor (PDGF) and Transforming Growth
Factor (TGF) etc.
6. CONCLUSION
The concepts involving the molecular and
microscopic tissue changes that accompany
tooth movement have undergone path breaking
changes. Bone bending and generation of
piezoelectric signals were earlier thought of
as important keys to explaining cellular
differentiation and bone remodeling. Later
research substantiated the concepts of tooth
movement as a result of an inflammatory
reaction in response to applied forces and the
vital role of chemical mediators such as
cytokines, interleukins and growth factors.
Recent research also sheds light on the role of
RANKL and RANKL receptors as well as osteo-
protegerins in establishing a balance between
osteoblasts and activated osteoclasts thereby
controlling the amount as well as direction of
bone remodeling Biology of tooth movement
being such an enormous and interesting platform
can surely accomodate several new studies and
research endeavors. In summary, despite its
apparently solid and inert form, bone is probably
the most dynamic and complex of body tissues.
CONSENT
It is not applicable.
ETHICAL APPROVAL
It is not applicable.
COMPETING INTERESTS
Authors have declared that no competing
interests exist.
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