Inherited Dentin Defects

Hedgehog function

development and repair

Wnt10a function

odontoblast differentiation

Bmp4 / Tgf-β / Smad4 function

odontoblast polarization

Smad4 / Runx2 function

maintenance of odontoblast identity

Why can dentin continue to form throughout life, unlike enamel?

Odontoblasts persist as long as the tooth remains vital, while ameloblasts are lost after enamel formation

T/F: Dentin is harder than enamel

False

• Dentin is more radiolucent and more yellow than enamel

Which mineralized tissue forms first during tooth development: dentin or enamel?

Dentin forms first and promotes enamel crystal initiation

What is dentin made of?

50% mineral (carbonated HAP) by volume

30% organic matrix (type I collagen; 90%)

What is the major non-collagenous protein in dentin?

DSPP (dentin sialophosphoprotein)

What is the major protein in dentin?

type I collagen

Witkop’s 2 categories of inherited dentin defects?

• Opalescent dentin = dentinogenesis imperfecta (DGI)

  • DGI-I

  • DGI-II

  • DGI-III

• Rootless teeth = dentin dysplasia (DD)

  • DD-I

  • DD-II

which types of inherited dentin defects are Autosomal Dominant?

DGI-I

DGI-II

DGI-III

DD-I

DD-II

describe etiology of genetic classifications for dentin defects

• DGI-I = (COL1A1, COL1A2) osteogenesis imperfecta-associated collagen defect

• DD-I = etiology still not settled

• DGI-II, DGI-III, DD-II = DSPP mutation spectrum

What is DGI-I?

dental phenotype of osteogenesis imperfecta

causative genes: COL1A1, COL1A2

genes are classically associated with DGI-I / OI

COL1A1 and COL1A2

DGI-I has what color?

blue-brown

DD-I features?

• rootless teeth

• normal crowns

Which conditions are caused by DSPP mutations?

DD-II, DGI-II, and DGI-III

Where is DSPP expressed?

In preameloblasts, preodontoblasts, and odontoblasts.

2 structural domains of DSPP

DSP & DPP

What does DSP stand for, and what is its broad role?

Dentin sialoprotein; it helps mediate predentin mineralization

What does DPP stand for, and what is its broad role?

Dentin phosphoprotein; it is very acidic and important for dentin mineralization

disease mechanism for many DSPP mutations

Dominant negative effect due to mutant DSPP being retained in the ER and trapping normal DSPP

DSPP mutations =

DD-II, DGI-II, DGI-III

severity order of the DSPP spectrum?

DD-II (mildest) < DGI-II < DGI-III (most severe)

DGI-II features

An isolated dentin defect caused by DSPP mutation that affects teeth only

 teeth are blue gray/amber brown and opalescent

hallmark feature of DGI-III

Early multiple pulp exposures, especially in the primary dentition

key pattern of DD-II

• Primary teeth resemble DGI, but permanent teeth are much milder

• Thistle-tube pulp deformity

• bulbous crowns

DGI-__ is the most severe form

DGI-III

T/F: Dentin Dysplasia type I (DD-I) is an autosomal dominant condition caused by mutations in DSPP. The teeth have short roots with unusual mobility and early exfoliation

False: DD-I’s etiology is UNKNOWN! (not a result of DSPP mutation)

T/F: A major concern in patients with inherited dentin defects is a loss of vertical dimension caused by rapid attrition of the teeth. The treatment of choice is to place cast gold crowns on the permanent first molars soon after they have erupted at age 6.

False: treatment should be STAINLESS STEEL CROWNS! (cast crowns can lead to complete fracture at the gingival level in fragile teeth)

T/F: DSPP is expressed mainly by odontoblasts but is also transiently expressed by pre-ameloblasts. Expression of mutant DSPP with dominant negative effects in pre-ameloblasts is thought to account for the enamel defects sometimes associated with DGI.

True

the major concern is loss of _________ dimension due to rapid attrition

vertical

T/F: DSPP mutation can affect enamel too, not just dentin.

True