effect of light energy on gene expression and tooth movement · the rate of tooth movement is...
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Effect of light energy on gene
expression and tooth movement Stephen Yen, DMD, PhD
Difficult tooth movements
8 years-adulthood
I
CLASSIC TOOTH MOVEMENT MODEL
COMPRESSION
Osteoclastic activity
TENSION
Osteoblastic activity
The rate of tooth movement is
limited by the biology of tooth
movement not the mechanics.Harry Dougherty, ABO president
Surgically-supported tooth movement can
alter the biology of the bony compartment
which teeth must pass through. The RAP
response can be specific and alter the
anchorage equation.
MOVING SEGMENTS OF BONE WITH
ORTHODONTIC MECHANICS INSTEAD
OF TOOTH MOVEMENT
APPLICATIONS OF ALVEOLAR
CORTICOTOMIES AND OSTEOTOMIES
TO ORTHODONTIC TOOTH MOVEMENT
• To facilitate difficult tooth movements
• To alter the shape of the dental arch
• To accelerate tooth movement
BONY TRANSPORT TO CLOSE
ALVEOLAR CLEFT
BUCCAL VIEW OF APPLIANCE
Pre-
surgical
2 wks
5 wks
FACILITATE DIFFICULT TOOTH
MOVEMENTS
CLOSING LARGE PALATAL FISTULA
THAT CANNOT BE MANAGED BY
TONGUE GRAFTS
Buccal Corticotomies
After Bony
TransportAfter corticotomy
facilitated tooth
movement
THE PROBLEM OF INADEQUATE
VERTICAL DENTOALVEOLAR
DEVELOPMENT
“DOWNGRAFT” AND ANTERIOR
REPOSITIONING
OF LATERAL SEGMENTS TO CLOSE CLEFT
SPACE AND CORRECT VERTICAL
DENTOALVEOLAR HEIGHT
Osteotomies for 2D movement
OSTEOTOMY VS CORTICOTOMY
OSTEOTOMY VS CORTICOTOMY
MATERIALS AND METHODS
• Thirty Sprague Dawley rats
• Five groups of six animal
• corticotomy-assisted tooth movement (CO+TM
• corticotomy (CO)
• osteotomy-assisted tooth movement (OS+TM)
• osteotomy (OS)
• normal tooth movement (TM)
• spring-mediated mesial tooth movement of the maxillary first molar
CORTICOTOMY DESIGN
• L-shaped horizontal and vertical cuts to box the anterior maxillary molar teeth
OSTEOTOMY DESIGN• Similar cut to the corticotomy except anterior part for fragment stability
• Chisel for separation of segment
NESTED–ANOVA STUDY DESIGN
Corticotomy alone
Corticotomy with tooth movement
Osteotomy
Osteotomy with toothMovement
Tooth movement control
Split-mouthControl/variabledesign
Uncut cutCoronal rootMid-level root
Apical root
anterior
interradicular
posterior
MesialPalatal
MATERIALS AND METHODS
• Taking Images
• IMTEK high resolution microCT under sedation, V-Works 5.0(CyberMed,Korea) 3 D image analysis software
• after surgery
• 21 days after surgery
• 2 months after surgery
• Tooth movement
• Two days later : 100 gs-2 nickel titanium springs were activated
Mesial
Distal
Interadicular
Mesial palatal
Four Sites per level
Left maxilla
Buccal
CORTICOTOMY (CO)
3 weeks later
C
MR
A
CORTICOTOMY WITH TOOTH
MOVEMENT (CO + TM)
3 weeks later
OSTEOTOMY (OS)
3 weeks later
C
MR
A
OSTEOTOMY WITH TOOTH
MOVEMENT (OS + TM)
3 weeks later
C
MR
A
TOOTH MOVEMENT ONLY (TM)
3 weeks later
C
MR
A
Osteotomy
w/ Tooth movementCorticotomy
w/ Tooth movement
RAP DO
21 DAYS POST-SURGERYCorticotomy-assisted Tooth Movement
l
Absence of bone
Replacement tissue(unmineralized)
BONE VOLUME(SCANCO MICROCT HISTOMORPHOMETRY)
0
20
40
60
80
100
120
140
3 days 21 days 80 days
OSTM
OS
CO
COTM
Percent:Cut side/
Uncut control side
BONE VOLUME(SCANCO MICROCT HISTOMORPHOMETRY)
0
20
40
60
80
100
120
140
3 days 21 days 80 days
OSTM
OS
CO
COTM
Percent:Cut side/
Uncut control side
Human 1wk 6wks 12 wks
OSTEOCLAST CELL COUNT AT 3
TIME POINTS
VEGF
PCNA
Osteocalcin
TGF Beta 1
IMMUNOHISTOCHEMICAL MARKERS
DISTINCT STAGES OF COTM
• Day 3- Resorptive stage, inflammatory mechanisms
• Day 21 Replacement stage
• Day 60 Mineralization stage
Human period for rapid tooth movement is less than three months.
DECORTICATION MODEL(WILCKO
AND KANTARCI)
Deep enough to reach the marrow space
Decortication + Tooth Movement @ 6 weeks
CoronalApical
Micro-CT Scans
Rat Maxilla
Apical Apical
1/3rd
Coronal
1/3rd
Coronal
Decortication + Tooth Movement @ 6 weeks
bur marks osteopeniatooth
movement
Control vs Surgery
Micro-CT Scans
Rat Maxilla
ANABOLIC EFFECTS
Bone apposition increases by 46% at the
Lamina dura at 4 weeks after decortication
CATABOLIC EFFECTS: OSTEOLAST
COUNT
RESEARCH COLLABORATORS
• Won Lee : Catholic University, Seoul,
• Rex Moats, Gevorg Karapetyan: CHLA
• Lei Wang:,Lei DeLin: Xian
• Alp Kantarci: Forsyth Dental Center.
• Dennis-Duke Yamashita, USC
Grant support from Chalmer Lyons Academy and
AONA
IS THERE A NON-SURGICAL METHOD FOR
PRODUCING REGIONAL ACCELERATED
PHENOMENON AND AND ITS DENTAL EFFECTS?
LOW-LEVEL LASER THERAPY (LLLT) IS A MEDICAL
AND VETERINARY TREATMENT THAT USES LOW-
LEVEL LASERS OR LIGHT-EMITTING DIODES TO
ALTER CELLULAR FUNCTION.
IR AND RED LIGHT CAN PENETRATE SKIN TO
ANALYZE BLOOD CELLS
CELL PROLIFERATION RESPONSE
Photobiomodulation-Induced Orthodontic Tooth Movement
Susanne Chiari, Susan S. Baloul, Emilie Goguet-Surmenian, Thomas E.
Van Dyke, Alpdogan Kantarci
CHIARI ET AL.
ANIMAL DATA LOOKS PROMISING
• Laser tx produces faster tooth movement than LED
• Longer exposures produced faster tooth movement
• 855nm more effective than 625nm
• Slower movement with LED produced better bone-
higher bone regeneration at center of root(microCT,
histology, ), less resorptive activity at a distance from
target, more bodily movement of root apices
HOW DOES LIGHT EFFECT CELLS?
MARROW STROMAL FIBROBLAST CELLS ISOLATED
FROM HUMAN BONE MARROW
• Marrow stromal fibroblast stem cells from Human bone marrow
• Isolates-clones
• Primary cell cultures
• Custom light arrays
light energy(joules/cm square)
(rep 1) (rep 2) (wavelength)
W930X137 C none 0 no light
W931X138 I-0.5 infrared 0.5 830nm
W932X139 I-1.0 infrared 1.0
W933X140 I-1.5 infrared 1.5
W934X141 I-2.0 infrared 2.0
W935X142 R-0.5 visible red 0.5 633nm
W936X143 R-1.0 visible red 1.0
W937X144 R-1.5 visible red 1.5
W938X145 R-2.0 visible red 2.0
Study design
This slide last updated 14 Apr 2011
BRDU LABELING OF CELL PROLIFERATION
IR Effect on
Cell Proliferation
Unlit Control culture
Maximum was a 40% difference in labeling
WESTERN BLOT AND REAL TIME PCR DATA
• OCN, Runx2, Alk Phosphatase
• GAPDH, Beta Actin controls for normalizing data
WESTERN BLOT(PROTEIN)C R0.5 R1.0 R1.5 R2.0 I0.5 I1.0 I1.5 I2.0
B-actin
+++ ++ ++ ++ ++ ++ ++ +++ +++
ALP
++ ++ ++(-) +++ + + ++ ++- +
RUNX-2
++ ++(+) ++ +++ + ++ ++ ++ +-
OCN
+++ ++ + +- +- +- +- ++ ++
Results were equivocal, some conditions showed subtle differences, no pattern detected.
This slide last updated 14 Apr 2011
Unlit Control IR illuminated
Human exon
Microarray
1,432,143 probe
Selection regions
40 probes per gene
22,011 protein
encoding genes
Affymetrix 1.0 ST
Human Exon array
Microarray to compare mRNA content in cells
Visible red light deregulates more genes than
infrared light
This slide last updated 14 Apr 2011
ANOVA identified the following number of
significantly deregulated genes vs control
(p<0.05 with false discovery rate
correction):
energy infrared visible red
0.5 299 1,210
1.0 7 27
1.5 166 4
2.0 24 1,900
Total 418 2,612
infrared visible
red
0.5
1.0
1.5
2.0
147152 1,063
25 25
2164 2
186 1882
Gene deregulated by either wavelength
at each energy level
This slide last updated 14 Apr 2011
Genes deregulated by either wavelength
This slide last updated 14 Apr 2011
R 0.5 R 2.0I 0.5 I 2.0
R 1.0 R 1.5I 1.0 I 1.5
Genes deregulated by infrared light Genes deregulated by visible red light
WHAT HAPPENS IF WE USE IR LIGHT WITH
PATIENT WHO JUST HAD SURGERY?
Key stages in bone response during fracture repair
IL1A
Involved in immune response
pro-collagen type I, III synthesis
5
7
log
2e
xp
ress
ion
10
9
0 I 0.5 I 1.0 I 1.5 I 2.0 R 0.5 R 1.0 R 1.5 R 2.0
6
8
This slide last updated 24 Mar 2011
MMP10
Involved in tissue breakdown and remodeling
This slide last updated 24 Mar 2011
5
6
log
2e
xp
ress
ion
8
7
0 I 0.5 I 1.0 I 1.5 I 2.0 R 0.5 R 1.0 R 1.5 R 2.0
TIMP1(Inhibitor of MMPs)
13.0
13.4
log
2e
xp
ress
ion
15.0
13.8
0 I 0.5 I 1.0 I 1.5 I 2.0 R 0.5 R 1.0 R 1.5 R 2.0
13.2
13.6
This slide last updated 02 May 2011
14.0
14.4
14.8
14.2
14.6
TNFSF11 (RANKL)
a key factor in osteoclast differentiation
6.0
6.4
log
2e
xp
ress
ion
8.0
6.8
0 I 0.5 I 1.0 I 1.5 I 2.0 R 0.5 R 1.0 R 1.5 R 2.0
6.2
6.6
This slide last updated 02 May 2011
7.0
7.4
7.8
7.2
7.6
TNFRSF11B (OPG)
Decoy receptor of RANKL
8
log
2e
xp
ress
ion
11
9
0 I 0.5 I 1.0 I 1.5 I 2.0 R 0.5 R 1.0 R 1.5 R 2.0
This slide last updated 02 May 2011
10
MICROARRAY DATA FOR MMP10, IL1A, TGF BETA
1 WERE CONFIRMED WITH QUANTITATIVE PCR
• RNA concentration was determined by NanoDrop 2000. RNA quality check was performed using BioAnalyzer 2100; RNA samples had a RIN range of 9.10 to 9.40. Reverse Transcription reaction was performed using RT2 First Strand Kit (Technical triplicates were performed using RT2 Primer Assays shown in the table below with 500 ng per reaction.
• RT-PCR was performed using the ABI 7900 in 384-well format. Ct values were normalized using the average Ct value of ACTB and GAPDH.
This slide last updated 23 Jun 2011
Up-regulation
Down-regulation
The 126 IR genes, 2,320 VR genes, and 292 genes were uploaded into Ingenuity Systems’
Pathway Analysis 9.0.
GENE PATHWAY STIMULATED BY VR LIGHT
2,320 VR genes: top networks
Genes in this network are shown in the following slide.*
*
This slide last updated 23 Jun 2011
Skeletal and muscular system development and
Function, tissue development, amino acid
Metabolism-consistent with bone turnover
INFRA RED(IR) GENE DEREGULATION 833 NM
This slide last updated 22 Jun 2011
Gene pathways stimulated by IR light
Extracellular
Space
Cell membrane
Cytoplasm
nucleus
This slide last updated 22 Jun 2011
126 IR genes: top 20 biological functions
Skin condition, genetic disorders, cancer,
immune response
DNA
DNA
RNA
Protein
Export
Function
DNA
RNA
Protein
Export
Function
Transcription-microarray, qPCR
POWER OF BIOINFORMATICS
This slide last updated 09 Apr 2012
0
500
1000
1500
2000
2500
3000
TGFB1 expression
W93
0
W93
1
W93
2
W93
3
W93
4
W93
5
W93
6
W93
7
W93
8
X13
7
X13
8
X13
9
X14
0
X14
1
X14
2
X14
3
X14
4
X14
5
C IR VR
0.5 0.5 1.0 1.0 1.5 1.5 2.0 2.0 0.5 0.5 1.0 1.0 1.5 1.5 2.0 2.0
exp
ress
ion
Protein Extraction from
cells, tissues, or bodily
fluids
Biotinylation of Proteins
Protein Conjugation to
Antibody Array
Detection by
Cy3-Streptavidin
ANTIBODY
ARRAY
ARRAY IMAGES TGF BETA PHOSPHO
ANTIBODY ARRAY
89
Control Sample I0.5 SampleR0.5 Sample
Akt1(Ab-72) Akt1(Ab-72)
633 nm visible red
Sma dependent TGF beta
pathway
visible red
Sma dependent TGF beta
pathway
visible red
Sma dependent TGF beta
pathway
infrared
infrared
830 nm
Akt pathway
ADDITIONAL PROTEIN ARRAY DATA
-0.2
-0.1
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
TGF B1 TGFB2 TGF B3 TGFB1RTGFb2R
control
VR0.5
IR0.5
TGF BETA PROTEINS
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
AKT1 Smad1 Smad2 Myc
Pathway components
C
VR0.5
IR0.5
-0.5
0
0.5
1
1.5
2
2.5
SEK1/MMK4 JNK PAK1,2,3 Rho/RacGNEF
control
VR0.5
IR0.5
NON-CANONICAL TGF BETA PATHWAYS
-0.4
-0.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
Akt mTOR PP2a
control
VR0.5
IR0.5
PTEN/AKT PATHWAY PROTEIN DATA
-1
-0.5
0
0.5
1
1.5
2
2.5
3
R0.5 vs C
R2 vs. C
I0.5 vs C
I2 vs. C
INFRARED 2.0 J/CM-SQ LARGEST PROTEIN
CHANGES
-1
-0.5
0
0.5
1
1.5
2
2.5
3
cd51 cd37 cd63 cd84
0.5VR
2.0vr
0.5IR
2.0IR
LEUKOCYTE CD ANTIGEN MARKERS
WHAT IS THE AKT1 PATHWAY?
Cell Culture Model of Hemifacial Hyperplasia and PTEN/mTOR Regulation
Craniofacial and Cleft Center
Children's Hospital Los Angeles
Stephen Yen D.M.D.,PhD.,
CHLA/Center for Craniofacial Molecular
Biology
Kiyomi Yamazaki, CCMB/USC
Charis Eng, Ohio State Univ & Cleveland Clinic
John Reinisch, M.D., CHLA
Sergei Kuznetsov, Ph.D. NIDCR/NIH
Pamela Robey, PhD. NIDCR/NIH
PROGRESSIVE DEFORMITY
“left swollen cheek” at birth
Sporadic occurrence
Asymmetric overgrowth of fat,
nerves, bone and teeth
Epidermal nevus
Asymmetric left forehead and face
Decreased animation of left face
Left eye presbyopia,
Frequent left chronic otitis media
(Turner, J.T., M.M.Cohen Jr.
and L.G.Biesecker 2004)
No involvement of extremities
No cerebriform folds
No invasive radiologic borders
larger teeth on the left side of the face
dental crossbites and open bite
left-sided enlargement of tongue
inferiorly displaced oral commisure
left tonsil hypertrophy
hypertrophic gingival and cheek mucosa
Histopathology. A, B Masson-Trichrome stain 10X and 40X. of dermis
showing abnormally thickened nerve trunks.
C, D. S100 antibody stain(10X and 100X showing abnormal Schwann cells
surrounding peripheral nerve axons and
increased number of nerves per area “neuromatous appearance
”. E. Hemotoxylin and eosin stain. Unaffected bone.
F.G. Affected bone showing increase width of cortical bone and
increased number of osteocytes.
METHODS
• Biopsy affected and unaffected sides during surgery
• Isolate marrow stromal fibroblasts
• Test clones for difference in cell size and number
• Microarray to screen for differences in gene expression
• Test candidate pathways with Western blots
Microarray analysis
Confirms same cell phenotype
Suggests 40% suppression of PTEN
In overgrown cells
Real time PCR confirms difference
In PTEN RNA compared to beta actin
PTEN TUMOR SUPPRESSOR GENE
Normal
Growth
PTEN mutation
-1059 C>G (Forward) -1059 C>G (Reverse)
WT (Forward) WT (Reverse)
Sequencing chromatogram of PTEN promoter mutation -1059 C>G
DNA SEQUENCING OF PTEN
PTEN PROMOTER MUTATION
Novel missense mutation lies between Erg-1 and p53 binding site
mTOR Rapamycin
S6K, sIF4E
HIF
Hamartoma formation
Tissue/ Organ hypertrophy
Autophagy
Rheb
Akt
P13K
TSC1/2
VHL
PTEN
AMPK
LKB1
Insulin, EGF, VEGF, FGF, TNF-a
IGF1,IGF 2, PDGF
Taken from Inoki et al., Nat Genetics 2005
mTOR Sirolimus(Rapamycin)
S6K, sIF4E
HIF
Hamartoma formation
Tissue/ Organ hypertrophy
Autophagy
Rheb
Akt
P13K
TSC1/2
VHL
PTEN
AMPK
LKB1
Multiple Growth factors
TSC(TSC1, TSC2)
Proteus syndrome
Cowden disease
BRRS
Proteus syndrome
Lhermite Dulcos Disease
Hemifacial hypertrophy
(PTEN)
VHL Disease
Familial Cardiac
Hypertrophy
Wolf-Parkinson-White
Syndrome
(PRKAG2)
Huntington
Disease(HD)
FUNCTIONAL EFFECTS AND
DOWNSTREAM SIGNALS
mTOR ps6K
mTOR Sirolimus
(rapamycin)
S6K, sIF4E
HIF
Hamartoma formation
Tissue/ Organ hypertrophy
Autophagy
Rheb
Akt
P13K
TSC1/2
VHL
PTEN
AMPK
LKB1
Insulin, EGF, VEGF, FGF, TNF-a
IGF1,IGF 2, PDGF
Taken from Inoki et al., Nat Genetics 2005
DECREASE IN CELL NUMBER
DECREASE IN CELL SIZE
DECREASE IN PROTEIN CONTENT
University of Southern California
Deborah Johnson
RNA polymerase
Stephen Yen
Axel Schonthal
Cell cycle analysis
Kiyomi Yamazaki
John Reinisch
Craig Cheung
John Walker
Dennis-Duke Yamashita
Ohio State University/Cleveland Clinic
Charis Eng
Xiou Ping Zhou
National Institute of Dental and Craniofacial Research
Pamela Robey
Sergei Kuznetsov
Lei Wang,
SINCE LIGHT CAN STIMULATE THIS PATHWAY, IR
LASERS SHOULD NOT BE USED IN PATIENTS
SUSPECTED OF HAVING CANCER, WHETHER
MALIGNANT OR BENIGN AS THE LASER IN THESE
WAVELENGTHS CAN HAVE A POTENTIATING
EFFECT.
IS THE CELL RESPONSE UNIVERSAL OR CELL-
TYPE SPECIFIC?
IMMEDIATE RESPONSE 10 MINUTES AFTER
ILLUMINATION
• Mesenchymal cell serum-free light
• Mesenchymal cell serum-free no light control
• Mesenchymal cell serum light
• Mesenchymal cell serum no light control
• Epithelial cell serum-free light
• Epithelial cell serum-free no light control
• Epithelial cell serum light
• Epithelial cell serum no light control
• NHEK-Neo keratinocyte(LONZO)
SIGNALING CASCADE
Time
early
late
SIGNALING CASCADE
Time
early
late
SIGNALING CASCADE
Time
early
late
SIGNALING CASCADE
Time
early
late
CYTOCHROMES 10 MINUTES AFTER
ILLUMINATION
HEAT SHOCK PROTEINS AFTER TEN MINUTES
COMMON REGENERATIVE MECHANISMS IN
EARLY DEVELOPMENT, REPAIR, AND CANCER
STEM CELLS LIVE IN MANY OF OUR TISSUES.
MANY MECHANISMS IN PLACE IN THE ADULT
MAYBE THE GOAL IS TO REACTIVATE AND
REGULATE THEM
TO BE ABLE TO TURN IT ON OR OFF IF
NECESSARY.
MODEL FOR HOW CELLS INTERACT WITH LIGHT
Dormant stem cell
Residing in adultReactivating pathways that
Pre-existCell re-steablishes homeostasis
With new pathways and functions
MODEL FOR HOW CELLS INTERACT WITH LIGHT
Dormant stem cell
Residing in adultReactivating pathways that
Pre-existCell re-steablishes homeostasis
With new pathways and functions
BONE
MODEL FOR HOW CELLS INTERACT WITH LIGHT
Dormant stem cell
Residing in adultReactivating pathways that
Pre-existCell re-steablishes homeostasis
With new pathways and functions
Dental pulp
MODEL FOR HOW CELLS INTERACT WITH LIGHT
Dormant stem cell
Residing in adultReactivating pathways that
Pre-existCell re-steablishes homeostasis
With new pathways and functions
Hair follicle
MODEL FOR HOW CELLS INTERACT WITH LIGHT
Dormant stem cell
Residing in adultReactivating pathways that
Pre-existCell re-establishes homeostasis
With new pathways and functions
Liver
The microarray and protein array experiments
• Demonstrates that each condition, each wavelength and energy level, will deregulate different sets of genes
• Allows us to target a particular cell response by picking the conditions and wavelength.
• Describe which sets of genes and pathways are stimulated by light
• Explains discrepancy in prior experimental data and literature
RANDOMIZED CLINICAL TRIAL: UNIVERSITY OF
ALABAMA, MAHIDOL UNIVERSITY
PRELIMINARY RESULTS OF BIOLUX
TS 1.5 INTRAORAL STUDY
April 24, 2013
THE STUDY
Randomized clinical trial funded by Biolux
Chung H Kau, Univ Alabama.
Amornpong Vachiramon, Mahidol University, Thailand
Tim Shaughessy, private orthodontist
The resulting dataset contains information and comparisons on three
groups: Control, Orthopulse ExtraOral, and Orthopulse IntraOral. There
were no significant demographic differences detected among the three
groups.
NC102267824
THE DATA
• Arch Level
• 21 female, 13 male
• 11 Control, 14 ExtraOral, 9 IntraOral
• 24 maxilla, 10 mandible
• Starting LII scores range from 3-14mm
• Age 11-27 (mean: 14)
• 26 Caucasians, 8 Other Ethnicities
• Data organized temporally as time-spells, yielding N=63
Dataid sex age ethnicity arch group LII_0 LII_F time rate
1 male 13 caucasian maxilla intraOral 5.7 0.0 17 2.35
2 female 17 caucasian maxilla intraOral 5.5 0.0 92 0.42
3 female 13 caucasian maxilla intraOral 6.0 0.0 21 2.00
4 male 14 chinese maxilla intraOral 12.1 0.0 50 1.69
5 female 14 hispanic maxilla intraOral 11.0 0.0 53 1.45
6 female 13 caucasian maxilla intraOral 3.6 0.0 40 0.63
7 female 12 caucasian maxilla intraOral 5.5 0.9 22 1.46
8 male 14 caucasian maxilla intraOral 14.2 0.8 50 1.88
9 male 11 caucasian maxilla extraOral 4.7 0.0 53 0.62
10 female 16 caucasian maxilla extraOral 4.5 0.0 42 0.75
11 female 13 caucasian maxilla extraOral 10.8 0.0 105 0.72
12 female 13 caucasian maxilla extraOral 7.6 0.0 31 1.72
13 female 14 caucasian maxilla extraOral 3.3 0.0 90 0.26
14 male 16 caucasian maxilla extraOral 9.5 0.0 66 1.01
15 male 12 caucasian maxilla extraOral 3.9 0.0 52 0.53
16 male 14 caucasian maxilla extraOral 4.9 0.5 55 0.56
17 female 14 caucasian maxilla extraOral 5.1 0.5 62 0.52
18 male 12 african maxilla extraOral 4.5 0.0 35 0.90
19 female 14 caucasian maxilla control 5.9 0.0 92 0.45
20 male 16 caucasian maxilla control 3.7 0.0 69 0.38
21 male 14 indian maxilla control 6.0 0.0 173 0.24
22 female 27 african maxilla control 3.8 0.5 161 0.14
23 female 11 asian maxilla control 6.6 0.7 105 0.39
24 female 15 caucasian maxilla control 4.2 1.8 118 0.14
25 female 18 chinese mandible intraOral 3.0 0.8 22 0.70
11 female 13 caucasian mandible extraOral 7.5 0.0 98 0.54
13 female 14 caucasian mandible extraOral 10.3 1.6 281 0.22
26 female 14 caucasian mandible extraOral 6.2 0.0 84 0.52
15 male 12 caucasian mandible extraOral 6.2 0.0 44 0.99
19 female 14 caucasian mandible control 7.4 0.3 111 0.45
27 male 11 caucasian mandible control 8.8 0.0 131 0.47
21 male 14 indian mandible control 5.7 2.2 149 0.16
28 female 13 caucasian mandible control 5.2 0.5 78 0.42
29 female 14 caucasian mandible control 6.6 2.9 104 0.25
0.14 0.14
0.24 0.26
0.38 0.39 0.420.45
0.52 0.520.56
0.62 0.63
0.720.75
0.90
1.01
1.45 1.46
1.69 1.72
1.88
2.00
2.35
0.5
11
.52
2.5
Ra
te (
mm
/we
ek)
Maxillary Individual Rates (mm/week)
Control ExtraOral IntraOral
0.32
0.72
1.400
.51
1.5
22
.5
Alig
nm
ent R
ate
(m
m/w
ee
k)
Control ExtraOral IntraOral
N Mean SD Min Max
Control 11 .318134 .1312198 .1423729 .470229
ExtraOral 14 .7189987 .3569368 .2566667 1.716129
IntraOral 9 1.398 .6729619 .4184783 2.347059
RESULTS
• IntraOral Treatment is statistically significant (at p<0.01)
• exp(2.196) ~ 9 times incidence of aligning when compared to Control
• ExtraOral Treatment marginally significant (at p<0.10)
• Peerapong Santiwong DDS, PhD
• Sivachat Chattawan DDS
• Amornpong Vachiramon DDS, DBA, MSc
Department of Orthodontics
Mahidol University
Thailand
Prospective Randomized Controlled Study
ORIGINALLY, A SPLIT-MOUTH CONTROL
DESIGN BUT IT WAS DISCOVERED THAT
LIGHT ACCELERATED BOTH SIDES DUE TO
CROSS-OVER SYSTEMIC EFFECTS SO THE
RESEARCH DESIGN CHANGED.
MB004 DailyFemale Age 31
Day 1 (12.52) 0.014 CuNiTi
Day 63 (4.49) 0.014x0.025
Day 84 (1.1) 0.014x0.025
1.99 2.51 0.27 7.17 0.58
0.81 0.22 0 2.88 0.58
0.65 0 0 0 0.45
1.33+0.68
0.96+0.27
0.56+0.24
0.00
0.50
1.00
1.50
2.00
2.50
Daily
Weekly
Control
Mean of Alignment Rate
Daily, Weekly & Control
Alig
nmen
t Rat
e (m
m/w
k)
n=7 n=7 n=6All Patients
Mean of Age
Male Female Total
Daily 20 (n=2) 23 (n=5) 22.14 (n=7)
Weekly 28 (n=2) 24 (n=5) 25.17 (n=7)
Control 32 (n=1) 20.56 (n=5) 25 (n=6)
Prospective Randomized Controlled Study
Photobiomodulation accelerates
orthodontic alignment in the
early phase of treatment
Chung How Kau, Alpdogan Kantarci, Tim Shaughnessy,
Amornpong Vachiramon, Peerapong Santiwong, Alvaro de
la Fuente, Darya Skrenes, Dennis Ma and Peter Brawn
Progress in Orthodontics 2013, 14:30
http://www.progressinorthodontics.com/content/14/1/
.
USC
U of Alabama
U Toronto
Harvard/Forsyth
Univ Sao Paulo
Kyunghee Univ
Mahidol Univ
Tel Aviv Univ
European Univ, DubaiErciyes University, Kayseri, Turkey.
Shandong
Univ
RESEARCH COLLABORATORS
• Won Lee : Catholic University, Seoul,
• Jeff Hammoudeh, Mark Urata, Cameron Francis, Rex Moats, Gevorg Karapetyan, CHLA
• Lei Wang, Lei DeLin: Xian
• Donald Ferguson: European University College, Dubai
• Songtao Shi, Anh Le, USC, Dennis Duke Yamashita USC
• Paul Matthews, optical engineer, formerly U Washington
• Guo Jie, Wangxing, Shandong University
• Alp Kantarci, Forsyth Dental Center
• Wang Huamin, West China University
• Anh Le, Songtao Shi, formerly CCMB now at U Penn
J Clin Orthod. 2016 May;
50(5):309-17
J Clin Orthod. 2016 May;50(5):309-17
J Clin Orthod. 2016 May;50(5):309-17
• 167 days
• 5.7 months
OUR CLINICAL APPLICATION IS TO ACCELERATE
TREATMENT IN CHILDREN WITH CLEIDOCRANIAL
DYSOSTOSIS-
THE POTENTIAL APPLICATIONS ARE:
ACCELERATED TOOTH MOVEMENT
ACCELERATED SURGICAL HEALING AND
STABILITY
ACCELERATED IMPLANT OSSEOINTEGRATION