L7 Flashcards
Enamel is a unique tissue due to its
high mineral content.
Proteins are necessary for enamel formation but are not part of the
final product.
The enamel structural proteins are cleaved by a
proteinase soon after their secretion into the matrix.
Enamel Formation Starts at the
Cusp Tip and Proceeds Cervically
Enamel starts as a
soft protein-rich tissue and matures into a virtually protein-free hard tissue.
MMP-20 cleaves
enamel matrix proteins during early enamel development.
Hydroxyapatite crystallites first grow in
length and later grow in width and thickness.
KLK4 cleaves enamel matrix proteins during
late enamel development so that the proteins can be removed from the matrix
The Maturation Stage
Enamel Proteinase
Kallikrein-4
The Secretory Stage
Structural Enamel Proteins
Amelogenin, Ameloblastin, Enamelin
Enamel Proteinase
Matrix Metalloproteinase-20
Spans Secretory and Maturation Stages
Intracellular Protein
Family with sequence similarity 83 member H
Syndromic Enamel Malformation
Secreted Protein
Family with sequence similarity 20 member A
Amelogenesis imperfecta (AI):
Hypoplastic: thin
(Secretory stage defects)
Hypomaturation: soft
(Maturation stage defects)
Hypocalcified: soft & thin
Maturation stage
acid formation occurs, rough ended. Smooth end is when acid is dispelled.
Amelogenin (AMELX: 85-90%): 18-25 kDa.
May regulate crystallite spacing, Mutations cause AI. On X chromosome.
Ameloblastin (AMBN:5-10%): 65-70 kDa glycosylated,
Accumulates in the sheath space. Human gene is on chromosome 4.
Enamelin (ENAM: 3-5%): 180-190 kDa,
highly glycosylated, intact enamelin is restricted to the mineralization front, Human gene is on chromosome 4.
Matrix Metalloproteinase (MMP20)
Enamelysin
Secretory stage
Processes enamel proteins
Kallikrein-4 (KLK4)
Serine Proteinase
Transition/Maturation Stages
Degrades enamel matrix
Enamel formation
different cohorts of cells occupy differnent locations in the cell.
Human AmelogeninGenes are on the
X and Y Chromosomes
AMELX Mutation (p.P52R) Causing
X-Linked AI
In general, AMELX mutations are associated with a
In general, AMELX mutations are associated with a smooth hypoplastic phenotype, but can also be associated with a hypomineralization/hypomaturation AI phenotype with discolored enamel.
Potentially more diagnostic than the pattern of inheritance (which may not be obvious in small families with few affected members) is the distinctive vertical banding pattern on the enamel of affected heterozygous females. The vertical bands are deposited because alternating bands of ameloblasts secrete normal or defective amelogenin after randomly inactivating either the defective or normal X-chromosome.
AMBN Exon 6 Deletion Causes
AI
The Ambn Phenotype
Autosomal Recessive Hypoplastic AI
Poorly Formed Rods (prisms)
Y chromosome amelogenin is
nonfunctional
The enamelin mutations result in enamel that is
hypoplastic. However, those heterozygous for the p.422fsX488 mutation have a mild phenotype consisting of localized pitting defects and those with the p.N197fsX227 mutation have a moderate phenotype consisting of grooves or shallow pits formed in parallel horizontal lines. When both alleles are defective, there is virtually no enamel layer.
Matrix Metalloproteinase-20 (MMP20) is expressed during
early enamel development and cleaves the secreted structural enamel matrix proteins including amelogenin, enamelin, and ameloblastin. Relative to the matrix proteins, MMP20 is present in trace amounts within the developing enamel matrix.
Ameloblastin has a
honeycomb pattern. If you stain for C-terminal part of protein, you see that it is on top. MMP20 cleaves these proteins to perform different functions in enamel.
Mmp20 Null Mouse Enamel has a
Weak Dentin-Enamel Junction
The MMP20 Phenotype
Five mutations caused pigmented hypomaturation AI and AI. In all five cases, the teeth were approximately normal in size, but the enamel layer did not contrast well with dentin on radiographs and the enamel tended to chip away from the underlying dentin.
Two mutations resulted in hypoplastic-hypomaturation AI
ameloblastin more important for
crystallite nucleation and growth, not just for ameloblasts.
The genes encoding amelogenin, ameloblastin, enamelin, & Mmp20 degenerate in mammals that have lost the ability to
make teeth during evolution (baleen whales). There is no selective pressure to maintain these genes except in making dental enamel.
Maturation Stage Enamel Proteins
that when Mutated can
Cause AI
Kallikrein 4 (KLK4)
Serine protease
Mutations cause autosomal-recessive AI
WD repeat protein 72 (WDR72)
Intracellular protein
Mutations caused autosomal-recessive AI
Chromosome 4 open reading frame 26 (C4orf26)
Secreted, somehow helps enamel to mature
Solute Carrier Family 24, Member 4 (SLC24A4)
Proton pump that may rid enamel of protons
Kallikrein-4 (KLK4) is expressed during
mid-late stage enamel development when the enamel has reached its full thickness and when proteins are actively removed from the hardening matrix. KLK4 degrades proteins to facilitate their removal from the enamel matrix.
Hunter-Schreger bands are the result of a
sectioning phenomenon through two enamel rod directions
The rod locates laterally and occlusally from its point of origin.
The purpose of the tortuous path of enamel rods is to dissipate the tremendous forces of mastication thus reducing the incidence of enamel fractures.
Hunter-Schreger bands are the result of a
sectioning phenomenon through two enamel rod directions
The rod locates laterally and occlusally from its point of origin.
The purpose of the tortuous path of enamel rods is to dissipate the tremendous forces of mastication thus reducing the incidence of enamel fractures.
Perikymata or Imbrication Lines
May be formed as crown becomes bigger and new cohorts of cells are added cervically to compensate for the increase in size.
Family with Sequence Similarity 83 member H (FAM83H) appears to be
ubiquitously expressed. Interestingly, FAM83H mutations only affect dental enamel. Mutations cause autosomal dominant hypocalcified amelogenesis imperfecta (ADHCAI).
Fam83H mutations cause
autosomal-dominant hypocalcified AI (ADHCAI) which is the most common form of AI in the United States. Individuals with FAM83H mutations may have enamel that is cheesy soft in consistency, light yellow in shade and nearly normal thickness.
However, the abraded teeth lose contour and often become tapered toward the incisal edge or occlusal surface. The abraded surfaces are rough in texture, take up stain rapidly, and are sensitive to thermal changes.
Family with sequence similarity 20, member A (FAM20A) is a
secreted glycoprotein.
Enamel Renal Syndrome
Delayed eruption
Pulp calcifications
FAM20A (17q24.2) Mutation
Enamel hypoplasia
Gingival hypertrophy
Kidney calicifications
The FAM20A mutation causes
hypoplastic amelogenesis imperfecta with associated gingival hyperplasia and kidney calcifications. Also present are intrapupal calcifications, delayed tooth eruption, and a failure of tooth development.
