BIOLOGY OF TOOTH

MOVEMENT

DR. LOHITH D
PG STUDENT
VSDCH
 CONTENTS

• INTRODUCTION
• HISTORY
• FUNDAMENTAL PRINCIPLES OF BIOLOGY OF TOOTH MOVEMENT
• DYAMIC BONE PHYSIOLOGY
• ORTHODONTIC TOOTH MOVEMENT
• TYPES OF FORCES
• BIOLOGIC CONTROL OF TOOTH MOVEMENT
-biologic electricity
-Pressure–tension effects in the periodontal ligament
space
• EFFECTS ON THE RESPONSE TO ORTHODONTIC FORCE
-Sequence of events
-Effects of force distribution
-Effects of force duration and force decay
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• TYPES OF ORTHODONTIC FORCES
• OPTIMAL ORTHODONTIC FORCE
• TISSUE RESPONSE IN PERIODONTIUM
• PHASES OF TOOTH MOVEMENT
• THEORIES OF TOOTH MOVEMENT
• TOOTH MOVEMENT AT CELLULAR AND MOLECULAR LEVEL
• SIGNALING MOLECULES INVOLVED IN REMODELING OF BONE
• LOCAL BIOLOGIC MEDIATORS OF ORTHODONTIC TOOTH MOVEMENT
• RANK/RANKL/OPG SYSTEM FOR CONTROL OF
OSTEOCLASTOGENESIS AND TOOTH MOVEMENT
• EFFECT OF DRUGS AND HORMONES ON ORTHODONTIC TOOTH
MOVEMENT
• ADVERSE EFFECTS OF ORTHODONTIC FORCE
• CONCLUSION
• REFERENCES
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 INTRODUCTION
• The eruption and movement of a tooth occurs due to the
translocation of the tooth from one position in the jaw to another.
• Teeth can be repositioned and retained in a new position using
orthodontic appliances, through the intervention of the cells of
the periodontium.
• Proper understanding of cellular and molecular biology will help
design mechanics that will produce maximum benefits during
tooth movement with minimal tissue damage.
• Orthodontic tooth movement is characterized by the creation of
compression and tension regions in the PDL.

BIOLOGY OF TOOTH MOVEMENT

112
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 HISTORY

• The earliest report on orthodontic tooth movement in the English

literature was published in 1911.
• Oppenheim admitted that all explanations of the mechanism of
tooth movement were hypotheses, and he laid out two
predominant theories.
1. the ‘old pressure theory of Schwalbe-Flouren’, which stated
that bone resorption takes place on the pressure side, with
deposition- on the tension side.
2. the movement of teeth was attributed to the ‘elasticity, the
compressibility and extensibility of the bone’. This theory was
not explained in detail.

Orthodontic Tooth Movement: A Historic Prospective

Front Oral Biol. 112
Basel, Karger, 2016, vol 18
• Historically, it has been found that when forces are applied,
three distinct phases of tooth movement can be observed,
namely

1. strain phase in which the PDL is squeezed (less than 5

seconds),
2. lag phase in which tooth movement pauses due to
hyalinization formed in the PDL (as long as 7-14 days),
3. move phase in which the tooth moves readily with significant
undermining resorption of the adjacent alveolar bone.

• Therefore, it is logical to assume that if the 2nd phase

(hyalinization in the PDL) can be avoided or minimized, the
tooth can move smoothly and faster.

Moving teeth faster, better and painless. Is it possible?

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Dental Press J Orthod 2010 Nov-Dec
 FUNDAMENTAL PRINCIPLES OF
BIOLOGY
OF TOOTH MOVEMENT
Periodontium
• The periodontium is composed of functionally coordinated
tissues.
• The specialized tissue that is the principal mediator of tooth
movement is the PDL.
• Assuming the periodontium is healthy and there is an adequate
band of attached tissue, orthodontic tooth movement is a viable
option.

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BIOLOGY OF TOOTH MOVEMENT
AEDJ.2015
• Each tooth is attached to and separated from adjacent alveolar
bone by a heavy collagenous structure, the periodontal
ligament(PDL).
• Normally it occupies approximately 0.5mm in width around all
parts of the root.

• Components of PDL:
1. Collagen fibres
2. Cellular elements; including osteoblast and osteoclast,
fibroblast, macrophages, cementoclast and undifferentiated
mesenchymal cells.
3.Vascular elements.
4.Neural elements.
5.The tissue fluids(ECM)

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Dynamic Bone physiology:
• As bone is a relatively rigid material, incapable of internal
expansion or contraction, changes in osseous structure are via
cell-mediated resorption and formation.

• Modeling, a change in shape or size of an osseous structure, is

achieved by differential bone formation and resorption along the
periosteal and endosteal surfaces.

• Internal turnover of osseous tissue is termed remodeling.

• Remodeling is controlled by both metabolic and biomechanical

mechanisms.

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112
Cell biology
• The structure of note is the cell membrane.

• This lipid bilayer separates the vast extracellular space outside

of the cell from the closed compartmentalized and highly
organized cytosol.

• The force system creates the movement of fluids in the

extracellular matrix. This event will alter the periodontal
ligament.

• These cells communicate with one another through the

liberation of specific molecules called chemokines and
cytokines.
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 ORTHODONTIC TOOTH MOVEMENTS
• Application of a force on the crown of the tooth leads to a
biological response in its surrounding tissues, resulting in an
orthodontic tooth movement, which depends on type,
magnitude, and duration of the force.

• Orthodontic forces comprise those that are meant to act on the

PDL and alveolar process, whereas orthopedic forces are more
powerful and act on the basal parts of the jaws.

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 Degree of tooth movement
before and after hyalinization.
Tooth movement occurring
after hyalinization is termed
secondary period

• If the duration of movement is divided into an initial and a

secondary period, direct bone resorption is found in secondary
period, when hyalinized tissue has disappeared after
undermining bone resorption.

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 BIOLOGIC CONTROL OF TOOTH
MOVEMENT
• Before discussing in detail the response to orthodontic force, it is
necessary to consider the biologic control mechanisms that lead
from the stimulus of sustained light force to the response of
alveolar bone remodeling that allows tooth movement.
• Two possible control elements, biologic electricity and pressure–
tension in the PDL that affects blood flow, are contrasted in the
two major theories of orthodontic tooth movement.
• The bioelectric theory relates tooth movement at least in part to
changes in bone metabolism controlled by biologic electricity that
are produced by light pressure against the teeth.

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• The pressure–tension theory relates tooth movement to
cellular changes produced by chemical messengers,
traditionally thought to be generated by alterations in blood
flow through the PDL and/or release of chemical messengers
from damaged cells in the PDL.
• Pressure and tension within the PDL, by reducing (pressure) or
increasing (tension) the diameter of blood vessels in the
ligament space, could certainly alter blood flow, and disruption
of cells occurs when soft tissues are stressed.

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 BIOLOGIC
ELECTRICITY
• Electric signals that might initiate tooth movement initially were
thought to be piezoelectric.
• Piezoelectricity is a phenomenon observed in many crystalline
materials in which a deformation of the crystal structure
created by external force produces a flow of electric current as
electrons are displaced from one part of the crystal lattice to
another.
• The piezoelectricity of many inorganic crystals, including those
in bone, has been recognized for many years.

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Piezoelectric signals have two unusual characteristics:
(1) a quick decay rate (i.e., when a force is applied, a piezoelectric signal is created in
response that quickly dies away to zero even though the force is maintained) and
(2) the production of an equivalent signal, opposite in direction, when the force is
released
• Both of these characteristics are explained by the migration of electrons within the
crystal lattice as it is distorted by pressure.
• When the crystal structure is deformed, electrons migrate from one location to
another and an electric current flow is observed.
• As long as the force is maintained, the crystal structure is stable and no further
electric events are observed.
• When the force is released, however, the crystal returns to its original shape, and a
reverse flow of electrons is seen.
• With this arrangement, rhythmic activity would produce a constant interplay of
current flows in one direction and then the other that would be measured as
amperes, whereas occasional application and release of force would produce only
occasional signal of this type.

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• There is no longer any doubt that piezoelectricity is important in
the general maintenance of the skeleton.
• Without such signals, bone mineral is lost and general skeletal
atrophy ensues—a situation that has proved troublesome for
astronauts, whose bones no longer flex in a weightless
environment as they would under normal gravity.
• Signals generated by the bending of alveolar bone during normal
chewing almost surely are important for maintenance of the bone
around the teeth.
• On the other hand, sustained force of the type used to induce
orthodontic tooth movement does not produce piezoelectric or
other types of stress-generated signals. As long as the force is
sustained, nothing happens.
• If stress-generated signals were important in producing the bone
remodeling associated with orthodontic tooth movement, a
vibrating application of pressure would be advantageous.
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 PRESSURE–TENSION EFFECTS IN THE
PERIODONTAL LIGAMENT SPACE
• Chemical messengers are known to be important in the cascade of
events that lead to remodeling of alveolar bone and tooth movement,
and both mechanical compression of tissues and changes in blood flow
can cause their release.
• There is no doubt that sustained pressure against a tooth causes the
tooth to shift position within the PDL space, compressing the ligament in
some areas while stretching it in others.
• The mechanical effects on cells within the ligament cause the release of
cytokines, prostaglandins, and other chemical messengers.
• In addition, blood flow is decreased where the PDL is compressed , while
it is maintained or increased where the PDL is under tension .
• These alterations in blood flow also quickly create changes in the
chemical environment. For instance, oxygen levels decrease on the
compressed area and carbon dioxide (CO2) levels increase, while the
reverse occurs on the tension side.
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These chemical changes, acting either 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:

(1)initial compression of tissues and alterations in blood flow
associated with pressure within the PDL,
(2)the formation and/ or release of chemical messengers, and
(3) activation of osteoblasts and osteoclasts, leading to remodeling
of alveolar bone.

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 EFFECTS ON THE RESPONSE TO
ORTHODONTIC FORCE
Sequence of Events

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What happens in the first hours after sustained force is placed
against a tooth, between the onset of pressure and tension in the
PDL and the appearance of second messengers a few hours
later?
• Experiments have shown that prostaglandin and interleukin-1
beta levels increase within the PDL within a short time after the
application of pressure, and it is clear now that both are
important mediators of the cellular response.
• Because prostaglandins are released when cells are mechanically
deformed, it appears that prostaglandin release is a primary
rather than a secondary response to pressure.
• At the molecular level, we are beginning to understand how
these effects are created. Focal adhesion kinase (FAK) appears to
be the mechanoreceptor in PDL cells, and its compression is at
least part of the reason that prostaglandin E2 (PgE2) is released.
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• Experiments have shown that concentrations of the receptor
activator of nuclear factor kappa-B ligand (RANKL) and
osteoprotegerin (OPG) in gingival crevicular fluid increase
during orthodontic tooth movement, which suggests that PDL
cells under stress may induce the formation of osteoclasts
through upregulation of RANKL.
• For a tooth to move, osteoclasts must be formed so that they
can remove bone from the area adjacent to the compressed
part of the PDL.
• Osteoblasts also are needed to form new bone on the tension
side and remodel resorbed areas on the pressure side.
• Prostaglandins have the interesting property of stimulating both
osteoclastic and osteoblastic activity, making them particularly
suitable as a mediator of tooth movement.

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• The course of events is different if the sustained force against the
tooth is great enough to totally occlude blood vessels and cut off
the blood supply to an area within the PDL.
• When this happens, rather than cells within the compressed area
of the PDL being stimulated, a sterile necrosis ensues within the
compressed area.
• In clinical orthodontics it is difficult to avoid pressure that
produces at least some avascular areas in the PDL, and it has
been suggested that releasing pressure against a tooth at
intervals, while maintaining the pressure for enough hours to
produce the biologic response, could help in maintaining tissue
vitality.
• This seems to be the mechanism by which chewing on a plastic
wafer or chewing gum after orthodontic force is applied reduces
pain—chewing force briefly displaces the tooth and allows a
spurt of blood into compressed areas, thereby reducing the size
of necrotic areas in the PDL.
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 EFFECTS OF FORCE DISTRIBUTION
• From the previous discussion, it is apparent that the optimum
force levels for orthodontic tooth movement should be just high
enough to stimulate cellular activity without completely occluding
blood vessels in the PDL.
• Both the amount of force delivered to a tooth and the area of the
PDL over which that force is distributed are important in
determining the biologic effect.
• The PDL response is determined not by force alone, but by force
per unit area, or pressure. Because the distribution of force
within the PDL, and therefore the pressure, differs with different
types of tooth movement, it is necessary to specify the type of
tooth movement as well as the amount of force in discussing
optimum force levels for orthodontic purposes.

112
• The simplest form of orthodontic movement is tipping. Tipping
movements are produced when a single force (e.g., a spring
extending from a removable appliance) is applied against the
crown of a tooth.
• When this is done, a tipping moment is created, and the tooth
rotates around its center of resistance, a point located about
halfway down the root.
• When the tooth rotates in this fashion, the PDL is compressed
near the root apex on the same side as the spring and at the
crest of the alveolar bone on the opposite side from the spring .
• Maximum pressure in the PDL is created at the alveolar crest
and at the root apex. Progressively less pressure is created as
the center of resistance is approached, and there is minimum
pressure at that point.

112
• If two forces are applied simultaneously to the crown of a tooth
so that there is no net tipping moment, the tooth can be moved
bodily (translated)—that is, the root apex and crown move in the
same direction the same amount.
• In this case, the total PDL area is loaded uniformly.

112
• In theory, forces to produce rotation of a tooth around its long axis
could be much larger than those to produce other tooth
movements, because the force could be distributed over the
entire PDL rather than over a narrow vertical strip.
• In fact, however, it is essentially impossible to apply a rotational
force so that the tooth does not also tip in its socket, and when
this happens, an area of compression is created just as in any
other tipping movement.
• For this reason, appropriate forces for rotation are similar to those
for tipping.

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• Extrusive movements ideally would produce no areas of
compression within the PDL, only tension.
• Like rotation, this is more a theoretical than a practical
possibility, because if the tooth tipped at all while being
extruded, areas of compression would be created.
• Even if compressed areas could be avoided, heavy forces in pure
tension would be undesirable unless the goal was to extract the
tooth rather than to bring alveolar bone along with the tooth.
• Extrusive forces, such as rotation, should be about the same
magnitude as those for tipping.

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• For many years, it was considered essentially impossible to
produce orthodontic intrusion of teeth.
• Now it is clear that clinically successful intrusion can be
accomplished, but only if very light forces are applied to the
teeth.
• Light force is required for intrusion because the force will be
concentrated in a small area at the tooth apex .
• As with extrusion, the tooth probably will tip somewhat as it is
intruded, but the force still will be concentrated at the apex.
• Only if the force is kept very light can intrusion be expected.

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 EFFECTS OF FORCE DURATION AND FORCE
DECAY
• The key to producing orthodontic tooth movement is the
application of sustained force, which does not mean that the
force must be absolutely continuous.
• It does mean that the force must be present for a considerable
percentage of the time, certainly hours rather than minutes per
day.
• As we have noted previously, animal experiments suggest that
only after force is maintained for approximately 4 hours do cyclic
nucleotide levels in the PDL increase, indicating that this duration
of pressure is required to produce the “second messengers”
needed to stimulate cellular differentiation.

112
• Clinical experience suggests that there is a threshold for force
duration in humans in the 4- to 8-hour range and that increasingly
effective tooth movement is produced if force is maintained for
longer durations.
• Although no firm experimental data are available, a plot of
efficiency of tooth movement as a function of force duration
would probably look like figure below.

112
• Duration of force has another aspect, related to how force
magnitude changes as the tooth responds by moving.
• Only in theory is it possible to make a perfect spring, one that
would deliver the same force day after day, no matter how
much or how little the tooth moved in response to that force.
In reality, some decline in force magnitude (i.e., force decay) is
noted with even the springiest device after the tooth has
moved a short distance .
• With many orthodontic devices, the force may drop all the way
to zero. From this perspective, orthodontic force duration is
classified by the rate of decay as:

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CONTINUOUS, INTERMITTENT AND
INTERRUPTED FORCES
Continuous force

112
interrupted force

112
intermittent force

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• Experience has shown that orthodontic appliances should not
be reactivated more frequently than at 3-week intervals.
• A 4- to 6- or 8-week appointment cycle is the usual minimum
in clinical practice, and now a 6- or 8-week cycle is more
typical.
• Undermining resorption requires 7 to 14 days (longer on the
initial application of force, shorter thereafter).
• When this is the mode of tooth movement and when force
levels decline rapidly, tooth movement is essentially complete
in this length of time.

112
• If the appliance is springy and light forces produce continuous
frontal resorption, there is no need for further activation for 6 to
8 weeks.
• If the appliance is stiffer and undermining resorption occurs, but
then the force drops to zero, the tooth movement occurs in the
first 10 days or so, and there is an equal or longer period for PDL
regeneration and repair before force is applied again.
• This repair phase is highly desirable and needed with many
appliances.
• Activating an appliance too frequently, short-circuiting the repair
process, can produce damage to the teeth or bone that a longer
appointment cycle would have prevented or at least minimized.

112
Optimal orthodontic force
• Traditionally, orthodontic forces have been categorized as “light”
or “heavy,”. To produce adequate biological response in the
periodontium, light forces are preferable.

• heavy forces often cause undermining bone resorption, and have

been implicated in root resorption.

• According to Schwarz, forces below optimum force produce no

reaction, whereas forces above that level lead to tissue necrosis,
thus preventing frontal resorption of the alveolar bone.
• optimal orthodontic force should not be greater than capillary
pulse pressure (20-26 gm/sq cm).

112 BIOLOGY OF TOOTH MOVEMENT

AEDJ.2015
Optimal Orthodontic forces
• In a purely mechanical system, acceleration is proportional to force.
Applying a greater force makes an object move faster.

• It is not the force applied at the bracket that is important

biologically, but the force per unit root surface that is transmitted at
the level of the periodontal ligament.

• The force per unit area decreases for a given applied force as the
amount of root surface increases. for a large, multirooted tooth, the
magnitude of force transmitted to the surrounding cells is less than
for a small, single rooted tooth in which the force is concentrated
over a lesser area.

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Tissue Response in Periodontium
INITIAL PERIOD OF TOOTH MOVEMENT

• Application of a continuous force on the crown of the tooth leads

to tooth movement within the alveolus that is marked initially by
narrowing of the periodontal membrane.

• osteoclasts differentiate along the alveolar bone wall, after 30 to

40 hours.

• All permanent alterations depend on cellular activity. The width

of the membrane is increased by osteoclastic removal of bone,
and the orientation of the fibers in the periodontal membrane
changes.
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HYALINIZATION PHASE
• During the initial application of force, compression in the
membrane frequently impedes vascular circulation and cell
differentiation, causing degradation of the cells and vascular
structures rather than proliferation and differentiation.

• The tissue reveals a glass like appearance in light microscopy,

which is termed hyalinization.

• It represents a sterile necrotic area, generally limited to 1 or 2

mm in diameter. The process displays three main stages:
 Degeneration
 elimination of destroyed tissue, and
 establishment of a new tooth attachment.

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112
DEGENRATION
• Degeneration starts where the pressure is highest and the
narrowing of the membrane is most pronounced.

• Electron microscopy has shown that cellular and vascular changes

may occur within a few hours of the application of the force.
Retardation of the blood flow is followed by disintegration of the
vessel walls and degradation of blood cells.

• The cells undergo a series of changes, starting with a swelling of the

mitochondria and the endoplasmic reticulum and continuing with
rupture of the membrane.
• This leaves only isolated nuclei between compressed fibrous
elements (pyknosis), which is the first indication of hyalinization.

112
• In hyalinized zones, the cells cannot differentiate into
osteoclasts and no bone resorption can take place.

• Tooth movement stops until the adjacent alveolar bone has

been resorbed, the hyalinized structures removed, and the
area repopulated by cells.

• A limited hyalinized area occurring during the application of

light forces may be expected to persist from 2 to 4 weeks in
a young patient. When high bone density is present, the
duration is longer.

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ELIMINATION OF DESTROYED TISSUE

• The peripheral areas of the hyalinized compressed tissue are

eliminated by an invasion of cells and blood vessels from the
adjacent undamaged PDL.
• The hyalinized materials are ingested by the phagocytic activity
of macrophages and are completely removed.

112
RE-ESTABLISHMENT

• Reestablishment of the tooth attachment in the hyalinized areas

starts by synthesis of new tissue elements as soon as the
adjacent bone and degenerated membrane tissue have been
removed.

• The ligament space is now wider than before treatment started,

and the membranous tissue under repair is rich In cells.

112
HYALINIZED ZONE AND ROOT RESORPTION

• A side effect of the cellular activity during the removal of the

necrotic hyalinized tissue is that the cementoid layer of the root
and the bone are left with unprotected surfaces in certain areas
that can readily be attacked by resorptive cells.

• Root resorption then occurs around this cell-free tissue, starting at

the border of the hyalinized zone . These initial injuries are small
and insignificant.

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SECONDARY PERIOD OF TOOTH MOVEMENT

• In this period, the PDL is widened. The osteoclasts attack the

bone surface over a much wider area.

• The fibrous attachment is reorganized by the production of new

periodontal fibrils.

• When the application of a force is favourable, a large number of

osteoclasts is seen along the bone surface and tooth movement is
rapid.

112
• The main feature is the deposition of new bone on the alveolar
surface from which the tooth is moving away;

• Cell proliferation (osteoblasts) is usually seen after 30 to 40

hours in young human beings.

• Shortly after cell proliferation has started, osteoid tissue is

deposited on the tension side.

• New bone is deposited until the width of the membrane has

returned to normal limits, and simultaneously the fibre system
is remodelled. the stretched fibres are not broken down to the
same extent as on the pressure side.

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• With bone deposition on the periodontal surface on the tension
side, an accompanying resorption process occurs on the
spongiosa surface of the alveolar bone. This maintains the
dimension of the supporting bone tissue. This occurs on the
pressure side too.

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HASES OF ORTHODONTIC TOOTH MOVEMENT

In 1962, Burstone suggested that, if the rates of tooth

movement were plotted against time, there would be 3
phases of tooth movement--

1. Initial phase,

2. Lag phase, and

3. Post lag phase.

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BIOLOGY OF TOOTH MOVEMENT
AEDJ.2015
 Initial phase

• Rapid tooth movement is observed over a short distance which then stops.

• Represents displacement of tooth in PDL membrane space.

• Both light and heavy forces displace tooth to same extent.

• Between 0.4 to 0.9mm usually occurs in a weeks time.

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 Lag phase

• Little or no tooth movement occurs.

• Formation of hyalinized tissue .

• Extent upto 2-3 weeks but may at times be as long as 10 weeks.

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 Post lag phase

• Tooth movement progresses

rapidly as the hyalinized zone is
removed and bone undergoes
resorption .

• Osteoclasts are found over a

larger surface area.

112
 Degree of tooth movement
before and after hyalinization.
Tooth movement occurring
after hyalinization is termed
secondary period

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• Pilon et al. divided the curve of tooth movement into four phases.

112
Biomarkers in orthodontic tooth movement
J Pharm BioAllied Sci 2015 Aug
 THEORIES OF TOOTH MOVEMENT
• The 3 main mechanisms for tooth movement proposes were :

1. Pressure-tension theory

2. Fluid dynamic theory

3. Bending of the alveolar bone

BIOLOGY OF TOOTH MOVEMENT

112 AEDJ.2015
The pressure-tension theory
• Classic histologic research about tooth movement by
Sandstedt (1904), Oppenheim (1911), and Schwarz (1932) led
them to hypothesize that a tooth moves in the periodontal
space by generating a “pressure side” and a “tension side.”

112
2. Fluid Dynamic
theory
2)Alteratio 3)Change in
• Given by Bien in 1966, 1)Sustaine oxygen level
also called blood flow n in blood and other
d pressure
theory of tooth flow metabolites
movement occurs as a
result of alterations in
fluid dynamics in
periodontal ligament.

• Periodontal space is a 4)Chemic 5)Stimulate

6)Tooth
confined space and al cellular
movem
passage of fluid in and out messenge differentiatio
ent
of this space is limited. rs n

112
3. The bone-bending theory
• Farrar, in 1876, suggested that alveolar bone bending plays a
pivotal role in orthodontic tooth movement.

• when an orthodontic appliance is activated, forces delivered to

the tooth are transmitted to all tissues near force application.

• These forces bend bone, tooth, and the solid structures of the
PDL.

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 MESSENGER SYSTEMS
First messengers

• Interleukin-1, Interleukin-6, Interleukin-11, Tumor necrosis factor, Osteoclast

differentiating factor, Bone formation IL-4, IL-13, IL- 18, Interferon, Osteoprotegrin
Cytokines

• Insulin-like growth factors I & II , Transforming growth factor , Fibroblast

growth factor, Platelet derived growth factor , Connective tissue growth
Growth factors
factors
• Polypeptides, Parathyroid hormones , Calcitonin, Insulin, Growth hormone ,
Steroid, 1,25, dihydroxy vitamin D3, Glucocorticoids , Sex steroids ,Thyroid
Hormones hormones

Colony- • M-CSF, G-CSF, GM-CSF

stimulating
factors

• Prostaglandins, Leukotriens, Nitric oxide

Others
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 SECOND MESSENGERS
Sutherland and Rall established the second-messenger basis for
hormone actions in 1958.

They proposed that the first messenger binds to a specific receptor

on the cell membrane and produces an intracellular chemical
second messenger.

This second messenger then interacts with cellular enzymes

which evokes a response.

cAMP pathway
cGMP pathway
Inositol triphosphate (IP3) pathway

112
 PROSTAGLANDINS
• Prostaglandins are a group of chemical messengers belonging to
a family of hormones called eicosanoids (derived from
arachidonic acid).

• They have a direct action on osteoclasts in increasing their

numbers and their capacity to form a ruffled border and effect
bone resorption.

• PGE2 also stimulates osteoblastic cell differentiation and new

bone formation.

112
• Von Euler (1934) – prostate fluid.
• Important role in stimulating bone resorption.
• One of chief mediators of inflammation cause an increase in
intracellular cAMP and Ca++ accumulation.

Cell membrane phospholipid

phospholipase- A

ARACHIDONIC ACID

Cyclo-oxygenase pathway lipo-oxygenase pathway

PG2 thromoxane 112 (HETE) leukotrienes

• LEUKOTRIENES

• Leukotrienes(LTs) are also metabolites of arachidonic acid and are

potent stimulators of bone resorption(Meghji et al27 1988).

• Within minutes, as paradental tissues become progressively strained

by applied forces, the cells are subjected to other first messengers,
the products of cells of the immune and the nervous systems.

• The binding of these signal molecules to cell membrane receptors

leads to enzymatic conversion of cytoplasmic ATP and GTP into AMP,
and GMP, respectively.

• These latter molecules are known as intracellular second messengers

112
ROLE OF CYTOKINES

Cytokines mediate mechanically induced bone remodelling by-

• It is cytokine that transmits signals from osteoblasts to osteoclasts.

• Cytokines either activate osteoclasts or promote differentiation of the
precursor cells.
• Secondly, osteoclasts produce collagenase enzyme that resorbs
osteoid. Osteoclasts cannot resorb bone until the surface osteoid
layer is removed.

• Although cytokine is a potent stimulator of bone resorption, it can

also stimulate osteoblast proliferation.
• Therefore, whether resorption or formation, depends upon the
cytokines and functional state of the available target cells.

112
 TOOTH MOVEMENT AT THE CELLULAR AND
MOLECULAR LEVELS
• Orthodontic tooth movement beyond the constraints of the original tooth
socket requires the conversion of mechanical forces into biological signals
by mechanosensitive cells.
• This mechanotransduction of signals promotes intracellular
communication and allows for the coordinated cellular response of
alveolar bone modeling that occurs in response to orthodontic force.
• Orthodontic forces are likely perceived by cells as changes in substrate
strain, fluid flow shear induced stress, and/or oxygen tension.
• Osteoprogenitor cells, bone lining cells, and osteocytes sense orthodontic
forces and initiate a number of signaling pathways through mediators
such as Wnt, BMP, TNFα, IL1β, CSF-1, VEGF, and PGE2, etc.
• These factors subsequently lead to the recruitment, differentiation, and
activation of osteoblasts and osteoclasts to conduct the bone formative
and resorptive activities, respectively, needed for orthodontic tooth
movement.
112
MECHANOTRANSDUCTION MEDIATES THE BONE
MODELING RESPONSE TO ORTHODONTIC FORCE
• Mechanotransduction requires the application of a mechanical
load to tissue, conversion of that load into a mechanical signal
that can be sensed at the cellular level, and cellular
transformation of the mechanical signal into a biochemical signal
that is then communicated to other cells to elicit a coordinated
cellular response.
• In the context of orthodontic tooth movement,
mechanotransduction very likely involves alveolar bone
osteocytes, bone lining cells, and PDL mesenchymal precursor
cells.
• Orthodontic forces move a tooth initially within the PDL space.
• This tooth movement likely results in mechanical strain changes in
PDL fibers and in underlying alveolar bone, as well as changes in
fluid flow within the lacunar–canalicular alveolar bone network
and within the PDL space. 112
• Tooth movement can also compress PDL blood capillaries resulting
in localized hypoxia.
• Once initiated, mechanotransduction leads to the activation of
downstream cell signaling pathways and cellular responses that
lead to bone resorptive and formative activities.
• Briefly, it is now recognized that the primary bone cell type
responsible for sensing mechanical load is the osteocyte rather
than the osteoblast.
• When mechanical loads are applied to tissue, shear stress or
strains are produced around cells.
• Significant evidence exists that mechanical forces applied to bone
lead to interstitial fluid flow within the lacunar–canalicular
network, Fluid flow is sensed by osteocytes as shear stress.

112
• At present, the precise molecular mechanisms involved in
mechanically induced osteocyte excitation are not completely
clear, but abundant evidence has suggested that multiple factors
and pathways are involved, such as integrins (cell to extracellular
matrix adhesion molecules), cytoskeletal structural proteins,
purinergic receptors, connexin 43 hemichannels, stretch-
sensitive ion channels, voltage-sensitive ion channels, and/or
primary cilia.
• Soluble factors released by osteocytes may also play a role in this
process known as autocrine stimuli.

112
• After sensing the mechanical load, osteocytes send signals to
other cells to regulate osteogenesis and osteoclastogenesis.
• Complex molecular mechanisms are involved in these
mechanotransduction processes, which researchers are just
beginning to understand.
• Recent findings have indicated that osteocyte-mediated
mechanotransduction is induced by the Wnt signaling pathway
but inhibited by the sclerostin (SOST) pathway through gap-
junction intercellular communications and/or extracellular
cytokines,or through soluble factors such as prostaglandins
released by osteocytes in a paracrine fashion.

112
• In addition to the osteocyte-mediated mechanism, mechanical
force can also directly stimulate osteoblasts and their progenitor
cells by producing strain (deformation) within the tissues where
these cells reside.
• As detailed in a recent review, mesenchymal stem cells can sense
mechanical strain through their cytoskeleton, focal adhesions,
and primary cilia.
• Tissue strain-induced cell stretching can induce the osteoblastic
differentiation of preosteoblasts via integrin/focal adhesion
kinase signaling and mechanosensitive calcium channels.
• At the molecular level, mechanotransduction by mesenchymal
stem cells may involve several pathways, including mitogen-
activated protein kinase (MAPK), Wnt, and RhoA/Rho kinase
signaling pathways.

112
• The PDL space is also fluid filled, such that the application of
orthodontic force leads to fluid-flow changes within the PDL
space.
• Shear stress from fluid flow can stimulate mesenchymal precursor
cell (such as PDL cells) Ca2+ signaling, which in turn promotes ATP
release, the production of prostaglandin E2 (PGE2), and the
proliferation of precursor cells.
• Notably, studies indicate that NO synthase (the enzyme that
synthesizes NO) and IL1β are also critical mediators of
orthodontic tooth movement.
• These mechanisms could potentially explain the differentiation of
PDL preosteoblasts into osteoblasts and initial mineralization
along stretched PDL fibers following orthodontic tooth
movement.

112
112
112
LOCAL BIOLOGICAL MEDIATORS OF
ORTHODONTIC
TOOTH MOVEMENT

112
LOCAL BIOLOGICAL MEDIATORS OF ORTHODONTIC TOOTH MOVEMENT

112
112
 RANK/RANKL/OPG SYSTEM FOR CONTROL OF
OSTEOCLASTOGENESIS AND TOOTH
MOVEMENT

• The regulation of osteoclastogenesis by osteoblasts is mediated

in large part by the nuclear factor kappa B ligand (RANKL)/
nuclear factor kappa B (RANK)/osteoprotegerin (OPG) ligand–
receptor complex.
• RANKL is found on the surface of osteoblast lineage cells where it
stimulates osteoclastogenesis by binding to receptor nuclear
factor kappa B (RANK), a transmembrane protein located on
osteoclast progenitors and osteoclasts.
• The binding of RANKL to RANK is essential for stimulating
osteoclast formation and activity and for promoting osteoclast
survival.

112
• The interaction of RANKL with RANK is regulated by the soluble
decoy receptor OPG, which is secreted by cells of the osteoblastic
lineage and functions as a competitive inhibitor of RANKL.
• OPG competes with RANKL for RANK and therefore acts to inhibit
osteoclast differentiation, activity, and survival, hence
diminishing osteoclastogenesis.

112
Tooth, PDL space and supporting alveolar bone environment during
quiescence

112
Cellular mechanotransduction of applied orthodontic force

112
Extracellular biologic mediators induce cellular changes

112
Recruitment, differentiation and activation of osteoclast precursor
cells leads to alveolar bone resorption and tooth movement

112
FFECT OF DRUGS ON TOOTH MOVEMENT
Drugs Effects on bone Effects on tooth
metabolism movement

Aspirin ↓Bone resorption ↓Tooth movement

Diclofenac ↓Bone resorption ↓Tooth movement
Ibuprofen ↓Bone resorption ↓Tooth movement
Indomethacin ↓Bone resorption ↓Tooth movement
Acetaminophen unproven No influence

Corticosteroids ↑Bone resorption ↑Tooth movement

(chronic use)

Bisphosphonates ↓Bone resorption ↓Tooth movement

112
 EFFECTS OF HORMONES ON TOOTH
MOVEMENT
Effects on bone Effects on tooth
metabolism movement

Estrogen ↓Bone resorption unproven

Androgen ↓Bone resorption unproven

Thyroid hormones ↑Bone resorption ↑Tooth movement

↓Root resorption

Parathyroid hormones ↑Bone resorption ↑Tooth movement

Vitamin D ↑Bone resorption ↑Tooth movement

112
 ADVERSE EFFECTS OF ORTHODONTIC
• FORCE
Gingival inflammation
• Root resorption
• Pulpal reactions
• Pain
• Mobility

112
Gingival inflammation
• Fixed-appliance orthodontics has been shown to produce
deleterious effects on the periodontium, ranging from gingivitis to
bone loss.
• can evoke local soft tissue response. This response is mainly due
to plaque accumulation and the proximity of these attachments
to the gingival sulcus.
• Gingival recession

112
Root resorption
• Orthodontic force application can sometimes evoke excessive
resorption of root cementum, proceeding into the dentin, eventually
shortening the root length—a process called root resorption.
• Maxillary central incisors, are the most prone to the process, followed
by the maxillary molars and the canines.
• In the mandibular arch, the most prone teeth are the lateral and
central incisors.

Assessment of root resorption and root shape: periapical vs panoramic films.

112 The Angle orthodontist. 2001 Jun
112
112
Pulpal reactions
• Although pulpal reactions to orthodontic treatment are
minimal, there is probably a modest and transient
inflammatory response within the pulp, at least at the
beginning of treatment. This may contribute to the discomfort
that patients often experience for a few days after appliances
are placed, but the mild pulpitis has no long-term significance.
• There are occasional reports of loss of tooth vitality during
orthodontic treatment.
• Usually there is a history of previous trauma to the tooth, but
poor control of orthodontic force also can be the culprit.
• A large enough abrupt movement of the root apex could sever
the blood vessels as they enter.
• Loss of vitality has also been observed when incisor teeth were
tipped distally to such an extent that the root apex, moving in
the opposite direction, was moved outside the alveolar
process. 112
• Because the response of the PDL, not the pulp, is the key element
in orthodontic tooth movement, moving endodontically treated
teeth is perfectly feasible.
• Endodontic treatment may be necessary before orthodontics
after trauma at any age or in adults receiving adjunctive
orthodontic treatment .
• There is no contraindication to going ahead with orthodontics
soon after the pulp therapy, and severe root resorption would not
be expected.
• One special circumstance is a tooth that experienced severe
intrusive trauma and required pulp therapy for that reason.
• If such a tooth must be repositioned orthodontically, resorption
seems less likely if a calcium hydroxide fill is maintained until the
tooth movement is completed, and then the definitive root canal
filling is placed

112
Pain
• If appropriate orthodontic force is applied, the patient feels little or
nothing immediately. Several hours later, however, pain usually
appears.
• The patient feels a mild aching sensation, and the teeth are quite
sensitive to pressure, so that biting a hard object hurts.
• The pain typically lasts for 2 to 4 days, then disappears until the
orthodontic appliance is reactivated.
• At that point, a similar cycle may recur, but for almost all patients,
the pain associated with the initial activation of the appliance is
the most severe.

112
• The pain associated with orthodontic treatment is related to the
development of ischemic (hyalinized) areas in the PDL that will
undergo sterile necrosis.
• The increased tenderness to pressure suggests inflammation at
the apex, and the mild pulpitis that usually appears soon after
orthodontic force is applied probably also contributes to the pain.
• There does seem to be a relationship between the amount of
force used and the amount of pain: all other factors being equal,
the greater the force, the greater the pain.
• If the source of pain is the development of ischemic areas,
strategies to temporarily relieve pressure and allow blood flow
through compressed areas should help.
• In fact, if light forces are used, the amount of pain experienced
by patients can be decreased by having them engage in repetitive
chewing (of sugarless gum, a plastic wafer placed between the
teeth, and so on) during the first 8 hours after the orthodontic
appliance has been activated.
112
• It has been suggested that acetaminophen (Tylenol) should be a
better analgesic for orthodontic patients than aspirin, ibuprofen,
naproxen, and similar prostaglandin inhibitors because it acts
centrally rather than as a prostaglandin inhibitor.
• Based on clinical studies, it now is widely accepted that
acetaminophen and the over-the-counter NSAIDs are equally
acceptable for controlling pain over the 3 to 4 days after an
orthodontic appliance has been activated.
• Given the recently discovered potential for liver damage from
acetaminophen, the choice for orthodontic pain now has swung
toward the prostaglandin inhibitors, although neither type of drug
would be used for orthodontic pain in large enough quantities or
long enough to create problems.

112
Mobility

• Mobility is due to widening of PDL space during orthodontic

treatment and temporary disorganization of the fibers in the PDL.

• Excessive mobility indicates that there is heavy force acting on the

tooth.

• If the tooth becomes extremely mobile, force should be

discontinued until the mobility decreases to moderate levels.
Excessive mobility will usually correct itself without permanent
damage.

112
 Effect of cyclical forces on the periodontal ligament and
alveolar bone remodeling during orthodontic tooth
movement
Angle Orthod. 2014;84:297–303
Objective:
To investigate the effect of externally applied cyclical (vibratory) forces on
the rate of tooth movement, the structural integrity of the periodontal
ligament, and alveolar bone remodeling.

Methods:
Twenty-six female Sprague-Dawley rats (7 weeks old) were divided into
four groups:
•CTRL (unloaded),
•VBO (molars receiving a vibratory stimulus only),
•TMO (molars receiving an orthodontic spring only), and
• TMO+VB (molars receiving an orthodontic spring and the additional
vibratory stimulus).

112
In TMO and TMO+VB groups, the rat first molars were moved mesially for
2 weeks using Nickel-Titanium coil spring delivering 25 g of force.

 In VBO and TMO+VB groups, cyclical forces at 0.4 N and 30 Hz were

applied occlusally twice a week for 10 minutes.

Microfocus X-ray computed tomography analysis and tooth movement

measurements were performed on the dissected rat maxillae.

Results:
Cyclical forces significantly inhibited the amount of tooth movement. Tooth
movement caused a significant increase in osteoclast parameters on the
compression side of alveolar bone and a significant decrease in bone
volume fraction in the molar region compared to controls.

Conclusions:
Tooth movement was significantly inhibited by application of cyclical
forces.
112
 The expression and regulation of Wnt1 in tooth
movement–initiated mechanotransduction
Ei Ei Hsu Hlaing.et al, AJODO, AUGUST 2020

Introduction: The Wnt signaling pathway acts as a key regulator of

skeletal development and its homeostasis. However, the potential
role of Wnt1 in the mechanotransduction machinery of orthodontic
tooth movementinitiated bone remodeling is still unclear. Hence, this
study focused on the regulatory dynamics of the Wnt1 expression in
both the periodontal ligament (PDL) and osteocytes in vivo and in
vitro.
Methods: The Wnt1 expression in the orthodontically moved
maxillary first molar in mice was assessed at 0, 1, and 5 days, on both
the compression and tension sides. Primary isolated human PDL
(hPDL) fibroblasts, as well as murine long-bone osteocyte-Y4 (MLO-
Y4) cells, were exposed to continuous compressive force and static
tensile force.
112
• Results: The relative quantification of immunodetection showed
that orthodontic tooth movement significantly stimulated the Wnt1
expression in both the PDL and alveolar osteocytes on the tension
side on day 5, whereas the expression on the compression side did
not change.
• This increase in the Wnt1 expression, shown in vivo, was also noted
after the application of 12% static tensile force in isolated hPDL
fibroblasts and 20% in MLO-Y4 cells. In contrast, a compressive force
led to the attenuation of the Wnt1 gene expression in both Hpdl
fibroblasts and MLO-Y4 cells in a force-dependent manner. In the
osteocyte-PDL coculture system, recombinant sclerostin attenuated
Wnt1 in PDL, whereas the antisclerostin antibody upregulated its
gene expression, indicating that mechanically-driven Wnt1 signaling
in PDL might be regulated by osteocytic sclerostin.

• Conclusions: Our findings provide that Wnt1 signaling plays a vital

role in tooth movement–initiated bone remodeling via innovative
mechanotransduction approaches. 112
 ROLE OF OXYGEN SUPPLY IN MACROPHAGES IN A MODEL OF
SIMULATED
ORTHODONTIC TOOTH MOVEMENT
Agnes Schröder et al. July 2020
HINDWAI
• Apart from periodontal ligament fibroblasts, immune cells like
macrophages also play an important mediating role in orthodontic
tooth movement (OTM).
• Upon orthodontic force application to malpositioned teeth,
macrophages in the periodontal ligament get exposed to both
mechanical strain and hypoxic conditions (via a compression of
blood vessels).
• In this study, they have assessed the relative impact of
orthodontically induced mechanical strain and hypoxic conditions on
macrophages for the mediation and regulation of OTM.
Macrophages were stimulated with physiological orthodontic
compressive forces of 2 g/cm2 for 4 h and 24 h on gas-impermeable
or gas-permeable cell culture plates under normoxic or hypoxic cell
culture conditions.
112
• They quantified expression of genes involved in inflammation (Tnf, Il-
6, and Cox-2), extracellular remodelling (Mmp-9), and angiogenesis
(Vegf) by RT-qPCR.
• Furthermore, they analysed HIF-1α, prostaglandin-E2, and VEGF
protein expression via immunoblotting or ELISA.
• Mechanical strain and oxygen supply both differentially affected
expression of genes and proteins involved in inflammation and
angiogenesis.
• In this context, they found that HIF-1α protein levels were elevated
by combined mechanical strain and hypoxic conditions, whereas gas-
permeable plates providing sufficient oxygen supply prevented HIF-
1α stabilization at the protein level after pressure application on
macrophages.

112
• Their results thus indicate that macrophages involved in the
mediation of OTM are affected by and respond differently to
hypoxic conditions and mechanical compressive strain, which
occur concomitantly during OTM, than periodontal ligament
fibroblasts (PDLF), thus indicating different roles of these cells in
the regulation of OTM at the cellular-molecular level.
• They further observed that contrary to PDLF HIF-1α stabilization
in macrophages is rather induced via the decreased oxygen
supply associated with OTM than via mechanotransduction by
mechanical strain.

112
 CONCLUSION
• In the present era, we have reasonably good understanding of
the sequence of events involved in orthodontic tooth movement
at the tissue and cellular levels on both the tensile and
compression sides of the periodontium.

• Rapid advances in all biological fields have enabled us to better

understand the mechanisms involved in orthodontic tooth
movement.
• The growing knowledge on the response of our cells to
mechanical loads should illuminate useful paths in clinical
orthodontics and assist us in identifying and discarding harmful
methods of mechanotherapy to provide the best treatment to
the patient.

112
 REFERENCES
• Contemporary Orthodontics – Profitt ,Sixth Edition

• Orthodontics current principles and techniques –Graber, Vanarsdall,

Vig, Sixth Edition

• Biology of tooth movement aedj.2015

• Orthodontic tooth movement: A historic prospective front oral

biol. Basel, karger, 2016, vol 18.

• Moving teeth faster, better and painless. Is it possible? Dental

press j orthod 2010 nov-dec .

• Biomarkers in orthodontic tooth movement J Pharm BioAllied

Sci 2015 Aug

112
• Effect of cyclical forces on alveolar bone remodeling, periodontal
ligament during orthodontic tooth movement. Angle Orthod.
2014;84:297–303

• Treatment of pain after initial archwire placement . American Journal of

Orthodontics and Dentofacial Orthopedics. 2010 Mar

• Assessment of root resorption and root shape: periapical vs panoramic

films. The Angle orthodontist. 2001 Jun

• The expression and regulation of Wnt1 in tooth movement–initiated

mechanotransduction, Ei Ei Hsu Hlaing.et al, AJODO, AUGUST 2020.

• ROLE OF OXYGEN SUPPLY IN MACROPHAGES IN A MODEL OF

simulated ORTHODONTIC TOOTH MOVEMEnt, Agnes Schröder et al.
July 2020 HINDWAI

112
THANK YOU