Download The biology of orthodontic tooth movement part 2: modulating tooth

CONTINUING EDUCATION
The biology of orthodontic tooth movement
part 2: modulating tooth movement via nitric
oxide and prostaglandin production
Dr. Michael S. Stosich reviews the markers of bone cell activity that are intrinsic to the complex process of
bone modeling and remodeling
Modulation of bone for orthodontic
tooth Movement
In the ever complex process of bone modeling and remodeling, certain markers of
bone cell activity have been shown to act as
key players that in part govern the process.
Nitric oxide (NO) and prostaglandin (PGE2)
production have been used as parameters
in bone cell mechanosensitivity in the study
of bone remodeling. Turner, et al.,1 have
shown that NO and PGE2 act as mediators
in the bone formation process in vivo.
Loading bone cells mechanically is also
associated with an increased production of
PGE2.2 When nitric oxide synthase (iNOS)
is inhibited, the loading response in bone
ceases.3 This indicates the essential role of
NO in the early stages of bone remodeling.
The production of NO and PGE2 by
primary bone cells is dependent upon
applied stress. Bone cells might detect
mechanical signals through fluid flow, and
mechanical loading of bone causes flow
of interstitial fluid through the canalicular
network.4 Using cyclic strains, PGE2 nor
NO could be detected; however, under low
levels of fluid flow, rapid production of both
agents was induced.4 Bone cells treated
Michael S. Stosich, DMD, MS, MS, has performed
orthodontic and craniofacial reconstruction
work throughout the world, but his first priority
is his patients at iDentity Orthodontics in the
Chicagoland area. With educational credentials
and training twice that required of an orthodontist, Dr.
Stosich has published and lectured throughout the United
States and abroad. His sincere interest and dedication
toward the study of stem cell tissue engineering, combined
with a rare creativity toward scientific discovery, paved the
way for Dr. Stosich to serve as lead scientist in a variety
of studies. This yielded numerous publications that lead
to important advancements in craniofacial cases. His
achievements were also awarded by the National Institutes
of Health, which endowed grants toward future study. Dr.
Stosich is also faculty at the University of Chicago Medicine.
Dr. Stosich believes in giving back to the communities he
serves and focuses on charitable giving where it can do
the most good by treating underserved and unprivileged
children through his involvement in the Smiles Change Lives
foundation, Smiles for Service, and his work on the Chicago
craniofacial team. Dr. Stosich is also involved in local
community programs linking orthodontics to philanthropy.
[email protected]
xx Orthodontic practice
Educational aims and objectives
This article aims to identify markers of bone cell activity that have been
shown to act as key players in the process of bone modeling and remodeling.
Expected outcomes
Correctly answering the questions on page XX, worth 2 hours of CE, will
demonstrate the reader can:
• Identify the roles that nitric oxide (NO) and prostaglandin (PGE2)
production play in the process.
• Realize the therapeutic range of ultrasound in stimulation of bone
formation and osteoblast proliferation.
with pulsating fluid flow (PFF) of increasing
flow rate rapidly stimulate the production of
NO in a manner that is dose dependent5.
PGE2 production tended to be higher as
a result of increased shear stress on the
cells, which was achieved by increasing
the flow rate.5 These results offer sound
evidence for the importance of shear stress
as a stimulus on bone cell walls in the
process of bone cell mechanotransduction
remodeling.
Ultrasound stimulates NO and
PGE2 production of human
osteoblasts
Reher, et al.,6 have shown that in bone
repair both osteogenesis and angiogenesis
are essential, and it has been shown
that the therapeutic range of ultrasound
stimulates bone formation and osteoblast
proliferation, and stimulates the synthesis
of angiogenic factors, endothelial growth
factors, basic fibroblast growth factors,
and interleukin-8. The ultrasound may in
fact act like mechanical stress on the bone
and stimulate PGE2 and NO production,
which are essential for bone remodeling.
NO production in bone showed a marked
increase when treated with 45 kHz of
therapeutic ultrasound.
Furthermore, iNOS and L-NAA had an
inhibitory effect on the ultrasound therapy.
Similarly, higher levels of PGE2 were
detected when the bone was subjected
to ultrasound, and COX-2 inhibited PGE2
synthesis at a frequency of 45 kHz. These
results show that when bone is subjected
to a therapeutic range of ultrasound,
osteoblasts are stimulated to produce
NO and PGE2. The synthesis of PGE2
appears to be promoted by the inducible
cycloxygenase pathway (COX-2). It may
also be inferred that L-arginine is crucial in
the NO pathway.
It has been shown that NO and PGE2
are essential in the bone remodeling
process. The studies here support the idea
that varying forms of mechanical therapy,
be it from shear stress or ultrasound,
elucidate a prominent increase in NO and
PGE2 activity, which may in turn lead to
new possibilities for increasing turnover
time in bone remodeling, and potentially
more rapid orthodontic tooth movement. OP
References
1. Turner CH, Owan I, Jacob DS, McClintock R, Peacock
M. Effects of nitric oxide synthase inhibitors on bone
formation in rats. Bone. 1997;21(6):487-490.
2. Binderman I, Zor U, Kaye AM, Shimshoni Z, Harell
A, Sömjen. The transduction of mechanical force into
biochemical events in bone cells may involve activation of
phospholipase A2. Calcif Tissue Int. 1988;42(4):261-266.
3. Fox SW, Chambers TJ, Chow, JW. Nitric oxide as
an early mediator of the increase in bone formation by
mechanical stimulation. Am J Physiol. 1996;270(6 Pt
1):E955-E960.
4. Smalt R, Mitchell FT, Howard RL, Chambers TJ.
Mechanotransduction in bone cells: induction of nitric
oxide and prostaglandin synthesis by fluid shear
stress, but not by mechanical strain. Adv Exp Med Biol.
1997;433:311-314.
5. Bakker AD, Soejima K, Klein-Nulend J, Burger EH.
The production of nitric oxide and prostaglandin E(2)
by primary bone cells is shear stress dependent. J
Biomech.2001;34(5):671-677.
6. Reher P, Harris M, Whiteman M, Hai HK, Meghji S.
Ultrasound stimulates nitric oxide and prostaglandin E2
production by human osteoblasts. Bone. 2002;31(1):236241.
Volume 5 Number 1