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Philosophy of Teeth Eruption Philosophy of Teeth Eruption

Fahad AlsulaimaniFahad Alsulaimani BDS, MS, Cert Ortho, OFPD, DScBDS, MS, Cert Ortho, OFPD, DScKing Abdulaziz university , Faculty of DentistryKing Abdulaziz university , Faculty of Dentistry

Orthodontic DivisionOrthodontic Division

Saudi Dental Society Annual Meeting Saudi Dental Society Annual Meeting

IntroductionIntroduction

Tooth Eruption “Is defined as the relocation Tooth Eruption “Is defined as the relocation of tooth from its developmental position of tooth from its developmental position within the alveolar bone to its functional within the alveolar bone to its functional position in the oral cavity” position in the oral cavity” (Massler & Schour (Massler & Schour 19411941))

IntroductionIntroductionTooth eruption has been investigated Tooth eruption has been investigated since the beginning of the since the beginning of the 1919thth century. century. Investigators have examined tooth Investigators have examined tooth eruption in many animal models such aseruption in many animal models such aseruption in many animal models such as eruption in many animal models such as rodents, primates, doges, cats and pigs. rodents, primates, doges, cats and pigs. They have proposed several theories to They have proposed several theories to explain tooth eruption process explain tooth eruption process

Theories of Teeth EruptionTheories of Teeth Eruption

Vascular Pressure Vascular Pressure (Constant (Constant 19001900))

Pulpal Pressure Pulpal Pressure (Charles, T. (Charles, T. 19231923))

Alveolar Bone Remodelling Alveolar Bone Remodelling (Brash J.C. (Brash J.C. 19281928))

Root Elongation Root Elongation (Gowgiel (Gowgiel 19611961))

Periodontal ligament Periodontal ligament (Berkovitz and Thomas (Berkovitz and Thomas 19691969))

Dental Follicle Dental Follicle (Marks, S.C. Jr. (Marks, S.C. Jr. 19951995))

Vascular PressureVascular Pressure (Constant (Constant 19001900))

He suggested that the blood pressure from He suggested that the blood pressure from the tissue that lies between the developing the tissue that lies between the developing tooth and the bony jaw responsible for the tooth and the bony jaw responsible for the tooth eruptiontooth eruptiontooth eruption tooth eruption However, changing the blood flow the However, changing the blood flow the periodontal tissue did not change the periodontal tissue did not change the eruption rate. eruption rate. (Tayler and Butcher (Tayler and Butcher 19511951))

Pulpal PressurePulpal Pressure (Charles, T. (Charles, T. 19231923))

He thought that pressure generated by the He thought that pressure generated by the dental pulp was sufficient to push tooth dental pulp was sufficient to push tooth occlusally occlusally

However, pulpless teeth can erupt at the However, pulpless teeth can erupt at the same rate as the normal teeth same rate as the normal teeth ( Herzberg and ( Herzberg and Schour Schour 19411941) )

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Alveolar Bone RemodelingAlveolar Bone Remodeling (Brash (Brash J.C. J.C. 19281928))

He believed that alveolar bone was responsible He believed that alveolar bone was responsible for tooth eruption since the areas where teeth for tooth eruption since the areas where teeth are missing have deficiency in alveolar bone are missing have deficiency in alveolar bone However, during tooth movement the bony However, during tooth movement the bony g yg ypattern usually follows the direction of the tooth pattern usually follows the direction of the tooth and it is obvious that the orientation of the and it is obvious that the orientation of the periodontal ligament are to pull tooth not bone periodontal ligament are to pull tooth not bone In addition, the rate of bone growth is slower In addition, the rate of bone growth is slower than the of tooth. than the of tooth. (Hoffman and Schour (Hoffman and Schour 19401940))

Root ElongationRoot Elongation (Gowgiel (Gowgiel 19611961))

He suggested that root elongation was He suggested that root elongation was responsible for tooth eruption since it is coincide responsible for tooth eruption since it is coincide with tooth eruption with tooth eruption

H tl t th d t hi hH tl t th d t hi hHowever, rootless teeth do erupt which mean However, rootless teeth do erupt which mean that root elongation per se not required for tooth that root elongation per se not required for tooth eruption but it might accelerate it.eruption but it might accelerate it.In addition, tooth eruption completes before In addition, tooth eruption completes before completion of root. completion of root. (Marks. S. Jr. et al (Marks. S. Jr. et al 19851985))

Periodontal LigamentPeriodontal Ligament (Berkovitz and (Berkovitz and Thomas Thomas 19691969))

They have proposed that PDL is essential They have proposed that PDL is essential for the continuous eruption of rodent for the continuous eruption of rodent incisors incisors However irradiation to monkey's jaw hadHowever irradiation to monkey's jaw hadHowever, irradiation to monkey s jaw had However, irradiation to monkey s jaw had completely inhibited root and periodontal completely inhibited root and periodontal ligament development and teeth still ligament development and teeth still erupted erupted

Dental FollicleDental Follicle (Marks, S.C. Jr. (Marks, S.C. Jr. 19951995))

It is a thin, dense connective tissue that It is a thin, dense connective tissue that surround the crown of unerupted tooth surround the crown of unerupted tooth It separated from the enamel organ by It separated from the enamel organ by basement membrane and bone cell liningbasement membrane and bone cell liningbasement membrane and bone cell lining basement membrane and bone cell lining the crypt by loss vascular connective the crypt by loss vascular connective tissue tissue It found that it play a very important role in It found that it play a very important role in teeth eruption teeth eruption

Dental FollicleDental Follicle (Marks, S.C. Jr. et al (Marks, S.C. Jr. et al 19951995) cont. ) cont.

If the dental follicle is removed, teeth will If the dental follicle is removed, teeth will not erupt and there neither bone formation not erupt and there neither bone formation nor resorption around the tooth nor resorption around the tooth Conversely if the tooth is removed andConversely if the tooth is removed andConversely, if the tooth is removed and Conversely, if the tooth is removed and the follicle left intact, the follicle will the follicle left intact, the follicle will continue to erupt with normal bone continue to erupt with normal bone resorption and formation around the tooth resorption and formation around the tooth area area

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Dental FollicleDental Follicle (Marks, S.C. Jr. (Marks, S.C. Jr. 19951995))

They concluded that the dental follicle is the They concluded that the dental follicle is the crucial mediator in the selective resorption and crucial mediator in the selective resorption and formation of alveolar bone seen in the erupting formation of alveolar bone seen in the erupting teeth. teeth. The follicle serves as an endogenous source of The follicle serves as an endogenous source of Colony Stimulating FactorsColony Stimulating Factors--1 1 (CSF(CSF--11). They ). They suggested that it is not only important in the local suggested that it is not only important in the local recruitment of monocytes to the area but also recruitment of monocytes to the area but also regulate the entire eruption process regulate the entire eruption process

Changes in The Dental FollicleChanges in The Dental Follicle

PhysicalPhysical11) the CT change from loose to dense) the CT change from loose to dense22) Cell differentiation to periodontal ligament) Cell differentiation to periodontal ligament33) in fibroblast number) in fibroblast number44) in monocytes number) in monocytes number44) in monocytes number ) in monocytes number

BiochemicalBiochemical11) in the amount of collagen () in the amount of collagen (250250%)%)22) in the proteoglycan content () in the proteoglycan content (4545%)%)33) secretion of DF) secretion of DF--95 95 sialoproteinsialoprotein44) in metalloproteinases in the beginning of tooth eruption) in metalloproteinases in the beginning of tooth eruption

Cytokines Role in Tooth Cytokines Role in Tooth EruptionEruption

ILIL--11α α (( CSFCSF--1 1 & MCP& MCP--11expression) expression)

TNFTNF--α α (( apoptosis in the apical area , might regulate apoptosis in the apical area , might regulate incisor eruption) incisor eruption)

CSFCSF--1 1 ( ( MCPMCP--11expression and monocytes fusion, expression and monocytes fusion, (( p y ,p y ,accelerate osteoclast differentiation and development ) accelerate osteoclast differentiation and development )

TGFTGF--ββ11 (( ILIL--11& MCP& MCP--11 expression) expression)

EGF EGF (( ILIL--11& MCP& MCP--11 expression) expression)

MCPMCP--11

Eruption Pathway

Mechanism of tooth eruption

Dental Follicle

Bone

Osteoclasts

Monocytes

fusion

CSF-1

TGF-βEnamel Organ

EGF IL-1αUpregulated

y

Upregulated

recruitment

MCP-1

recruitment

enhancesenhances

enhances

Monocyte Chemoattractant Protein Monocyte Chemoattractant Protein ––1 1 (MCP(MCP--11))

Belong to CC family Belong to CC family Monomeric protein (Monomeric protein (76 76 a.a. from a.a. from 9999aa)aa)Murine MCPMurine MCP--11share about share about 6565% homology % homology

ith h MCPith h MCP 11with human MCPwith human MCP--11Bind to CCRBind to CCR2 2 receptorreceptorPotent monocytes chemoattractant Potent monocytes chemoattractant

MCPMCP--1 1 (cont.)(cont.)

Expressed by fibroblast, smooth muscle Expressed by fibroblast, smooth muscle cell, endothelial cells, osteoblast and cell, endothelial cells, osteoblast and monocyte/ macrophagemonocyte/ macrophageStimulated byStimulated by ILIL 11 ILIL 22 ILIL 66 TNFTNF αα LPSLPSStimulated by Stimulated by ILIL--11, IL, IL--22, IL, IL--66, TNF, TNF--αα, LPS, , LPS, INFINFγγ

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HypothesisHypothesis

MCPMCP--11 isis importantimportant chemokineschemokines ininteethteeth eruptioneruption

MCPMCP--11 isis importantimportant inin bonebone andandtissuetissue remodelingremodeling inin thatthat involvedinvolved inintoothtooth eruptioneruption..

Materials & MethodsMaterials & MethodsRate of Teeth EruptionRate of Teeth Eruption2828 litterslitters fromfrom bothboth MCPMCP--11 --//-- andand wildwild typetype newbornnewbornmicemice werewere analyzedanalyzed forfor incisorincisor andand molarmolar eruptioneruption..

EffectEffect ofof MCPMCP--11 onon ToothTooth EruptionEruptionEffectEffect ofof MCPMCP 11 onon ToothTooth EruptionEruption

A) Wild Type Group15 newborn mice (C57Bl6/J)

Sacrificed at three time points day 5,9,and 13

B) MCP-1 Group15 newborn MCP-1 knockout

mice were sacrificed at 3time points day 5, 9 and 13

Rate of Incisor EruptionRate of Incisor Eruption

Pecentage of incisor Eruption

90%100%110%

0%10%20%30%40%50%60%70%80%90%

Day 7 Day 8 Day 9 Day 10 Day 11 Day 12

Days

Per

cent

age

C57MCP-1

Rate of Molar Eruption Rate of Molar Eruption

Comparison of Molar Eruption Between C57B6/J and MCP-1 Mice

120%ar

0%20%40%60%80%

100%

Day 14 Day 15 Day 16 Day 17 Day 18

Days

Perc

enta

ge o

f Mol

Erup

tion

C56MCP-1

Monocytes In the Occlusal of Monocytes In the Occlusal of MCPMCP--1 1 Vs. WTVs. WT

BoneBone

Cusp

DF

Cusp

DF

Presence of Monocytes in the Presence of Monocytes in the Occlusal area / Follicular lengthOcclusal area / Follicular length

Monocytes distribution per follicular Length in occlusal area

**100

ular

*

*

0

20

40

60

80

Day 5 Day 9 Day 13

Time Points

Mea

n N

umbe

r/ fo

llicu

Leng

th (m

m)

WT.MCP-1

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Monocytes in the C.T. Area MCPMonocytes in the C.T. Area MCP--1 1 Vs. WTVs. WT

GingivaGingiva

CT CT

BoneBone

Monocytes in The Occlusal CTMonocytes in The Occlusal CT

Monocytes In The Occlusal Connective Tissue Area

*

120014001600

s/ A

rea

0200400600800

10001200

Day 5 Day 9 Day 13

Time Points

Mea

n of

Mon

ocyt

es(m

m2) WT.

MCP-1

Monocytes Recruitment in the Monocytes Recruitment in the Furcation Area MCPFurcation Area MCP--1 1 Vs. WTVs. WT

PulpPulp

BoneBone

Monocytes In The Furcation Monocytes In The Furcation Area /FLArea /FL

Monocytes distribution per Follicular Length in the Apical Area

120f h

020406080

100120

Day 5 Day 9 Day 13

Time Points

Mea

n N

umbe

r of

Mon

ocyt

es/

Folli

cula

r Len

gth

(mm

) WT.MCP-1

Osteoclast in The Occlusal Osteoclast in The Occlusal Area MCPArea MCP--1 1 Vs. WT Day Vs. WT Day 55

BoneBoneLacunae

CuspCusp

BoneDF

Presence of Osteoclast in the Presence of Osteoclast in the Occlusal area / Bone LengthOcclusal area / Bone Length

Presence of Osteoclast per Occlusal Bone Follicular Length

**20

one

0

5

10

15

Day 5 Day 9

Tim e Points

Mea

n of

ost

eocl

ast/

Bo

Leng

th (m

m)

WT

MCP-1

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Occlusal Osteoclastic Occlusal Osteoclastic Activity at Day Activity at Day 5 5

Osteoclastic Activity in The Occlusal Area at Day 5

**3 5

4

*

*

00.5

11.5

22.5

33.5

Shallow Medium Deep

Lacunae Type

Mea

ns o

f Lac

unae

WTMCP-1

Osteoclast in Furcation Day Osteoclast in Furcation Day 5 5 MCPMCP--1 1 Vs.WTVs.WT

PulpPulp

Furcation

Furcation

Bone

Bone

Osteoclast In the Furcation Osteoclast In the Furcation AreaArea

Osteoclastic activity in the Furcation area per bone length

121416

last

/ m

)

02468

1012

Day 5 Day 9 Day 13

time points

mea

ns o

f ost

eoc

bone

leng

th (m

WTMCP-1

Eruption Pathway

Suggested Mechanism of Tooth Eruption

Dental Follicle

Bone

Osteoclasts

Monocytes

fusionOPGL ?

CSF-1

TGF-βEnamel Organ

EGF IL-1αUpregulated

y

Upregulated

recruitment

MCP-1

recruitment

regulateregulate

regulae

modified from Wise GE 1998

regulate

Eruption Pathway

MY Suggested Mechanism of Tooth Eruption

Dental Follicle

Bone

Osteoclasts

Monocytes

fusionOPGL ?

CSF-1

TGF-βEnamel Organ

EGF IL-1αUpregulated

y

Upregulated

recruitment

MCP-1

recruitment

regulateregulate

regulate

modified from Wise GE 1998

regulate

ConclusionConclusion1. MCP-1 regulate incisor and molar eruption2. MCP-1 inhibit monocytes recruitment to the

occlusal and furcation areas during tootheruptioneruption

3. MCP-1 inhibit osteoclast formation during tootheruption

4. In the absence of MCP-1 over expression ofother eruption cytokines in a redundant factionto regulate teeth eruption

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Thank youThank youThank you Thank you

Presence of Monocytes in the Presence of Monocytes in the Occlusal areaOcclusal area

Monocytes Distribution in the Occlusal Area per Bone length

**80

010203040506070

Day 5 Day 9 Day 13

Time Points

mea

n nu

mbe

r of

Mon

ocyt

es /

Bon

e le

ngth

(mm

)

WT.MCP-1

Osteoclastic activity in the Osteoclastic activity in the furcation areafurcation area

Ostoclastic Activity in The Furcation Area

250

300

350

/ are

a

0

50

100

150

200

250

Day 5 Day 9 Day 13

Time Points

Mea

n of

Ost

eoca

lst

(mm

2)

WTMCP-1

Percentage of Eroded bone Percentage of Eroded bone SurfaceSurface

Pre centage of e rrode d Bone Surface in the occlus al are a

**.

8090

100

rcen

t

01020304050607080

Day 5 Day 9

Tim e Points

Mea

n of

Ero

ded

Bon

e Pe

WT

MCP-1

Monocytes Distribution in The Monocytes Distribution in The Furcation AreaFurcation Area

Monocytes Distribution per Follicular Bone Length in the Apical Area

100

020406080

100

Day 5 Day 9 Day 13

Time Points

Mea

n N

umbe

r of

Mon

ocyt

es/

Folli

cula

r Bon

e Le

ngth

(mm

)

WT.MCP-1

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Occlusal Osteoclastic activity at Occlusal Osteoclastic activity at day day 9 9

Osteoclastic Activity in The Occlusal Area at Day 9

3

3.5

e

0

0.5

1

1.5

2

2.5

Shallow Medium Deep

Lacunae Type

Mea

ns o

f Lac

unae

WTMCP-1