effect of light energy on gene expression and tooth movement · the rate of tooth movement is...

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