Enamel Formation and Amelogenesis Imperfecta

Hu, Jan C.‐C.; Chun, Yong Hee P; Hazzazzi, Turki Al; Simmer, James P.

doi:10.1159/000102683

Cited by 234 publications

(246 citation statements)

References 128 publications

(38 reference statements)

Supporting

Mentioning

220

Contrasting

Unclassified

Order By: Relevance

“…Such unique extracellular matrix composition of mantle dentin and aprismatic enamel at the DEB is likely to be essential for the proper formation and function of this interface. This notion is supported by the studies of the hereditary tooth diseases in humans and experiments with animal models, which demonstrate that mutations in a number of extracellular tooth proteins lead to the weakening of the DEB and the breaking off of tooth enamel leading to exposure of the dentin surface (45)(46)(47)(48)(49)(50). Hence, it is essential to understand how the individual proteins present at this boundary, as well as more complex systems including multiple ECM components, affect calcium phosphate mineralization.…”

mentioning

confidence: 89%

Amelogenin-Collagen Interactions Regulate Calcium Phosphate Mineralization in Vitro

Deshpande

Fang

Simmer

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Collagen and amelogenin are two major extracellular organic matrix proteins of dentin and enamel, the mineralized tissues comprising a tooth crown. They both are present at the dentinenamel boundary (DEB), a remarkably robust interface holding dentin and enamel together. It is believed that interactions of dentin and enamel protein assemblies regulate growth and structural organization of mineral crystals at the DEB, leading to a continuum at the molecular level between dentin and enamel organic and mineral phases. To gain insight into the mechanisms of the DEB formation and structural basis of its mechanical resiliency we have studied the interactions between collagen fibrils, amelogenin assemblies, and forming mineral in vitro, using electron microscopy. Our data indicate that collagen fibrils guide assembly of amelogenin into elongated chain or filament-like structures oriented along the long axes of the fibrils. We also show that the interactions between collagen fibrils and amelogenin-calcium phosphate mineral complexes lead to oriented deposition of elongated amorphous mineral particles along the fibril axes, triggering mineralization of the bulk of collagen fibril. The resulting structure was similar to the mineralized collagen fibrils found at the DEB, with arrays of smaller well organized crystals inside the collagen fibrils and bundles of larger crystals on the outside of the fibrils. These data suggest that interactions between collagen and amelogenin might play an important role in the formation of the DEB providing structural continuity between dentin and enamel.Dentin and enamel, the two mineralized tissues that comprise a tooth crown, are strikingly different in terms of their compositional, structural, and mechanical properties (1). Despite these differences, dentin and enamel work together for decades under severe mechanical stress, without delamination or catastrophic failure.Dentin is a mineralized tissue similar to bone, comprised primarily of fibrillar collagen type I, carbonated apatite and water (2). There are other so-called noncollagenous macromolecules present that, in total, represent less then 10% by mass of organic material, although they play important roles in the formation and function of these tissues. All bone materials share the same basic building block, a collagen fibril, in which plateshaped apatitic crystals are organized in parallel arrays with their c-axes co-aligned with the long axis of the fibril (2-4). Collagen type I triple helical molecules, are super-coiled assemblies of two identical ␣1-chains and one ␣2-chain with a different sequence (5, 6). Each chain contains more than 1000 amino acids and is primarily composed of Gly-X-Y repeats, where amino acids proline (Pro) and hydroxyproline (Hyp) predominantly occupy X and Y positions. All three chains in the molecule adopt a polyproline II (PPII)-like structure, which is stabilized by direct and water mediated inter-and intra-chain hydrogen bonds (5, 6). Collagen fibrils form via a self-assembly process in which collag...

show abstract

mentioning

confidence: 89%

Amelogenin-Collagen Interactions Regulate Calcium Phosphate Mineralization in Vitro

Deshpande

Fang

Simmer

et al. 2010

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…During the secretory stage of amelogenesis, ameloblasts secrete different proteins into the enamel extracellular matrix, including AMLX and AMBN, which comprise about 95% to 97% of the organic matrix in the secretory stage (15). Therefore, we investigated the expression levels of AMLX and AMBN after miR-224 mimic and inhibitor transfection.…”

Section: Resultsmentioning

confidence: 99%

MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization

Fan

Zhou

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

Enamel mineralization is accompanied by the release of protons into the extracellular matrix, which is buffered to regulate the pH value in the local microenvironment. The present study aimed to investigate the role of microRNA 224 (miR-224) as a regulator of SLC4A4 and CFTR, encoding the key buffering ion transporters, in modulating enamel mineralization. miR-224 was significantly downregulated as ameloblasts differentiated, in parallel with upregulation of SLC4A4 and CFTR. Overexpression of miR-224 downregulated SLC4A4 and CFTR expression in cultured human epithelial cells. A microRNA luciferase assay confirmed the specific binding of miR-224 to the 3= untranslated regions (UTRs) of SLC4A4 and CFTR mRNAs, thereby inhibiting protein translation. miR-224 agomir injection in mouse neonatal incisors resulted in normal enamel length and thickness, but with disturbed organization of the prism structure and deficient crystal growth. Moreover, the enamel Ca/P ratio and microhardness were markedly reduced after miR-224 agomir administration. These results demonstrate that miR-224 plays a pivotal role in fine tuning enamel mineralization by modulating SLC4A4 and CFTR to maintain pH homeostasis and support enamel mineralization.

show abstract

“…10 Amelogenesis is a tightly regulated process in which ameloblasts express LM-332. 3 Replacement of the lamina basale during amelogenesis is impaired if LM-332 is altered. 3 Enamel and skin apparently respond differently to heterozygous mutations affecting the α chain, because skin fragility was absent in carriers.…”

Section: Discussionmentioning

confidence: 99%

“…3 Replacement of the lamina basale during amelogenesis is impaired if LM-332 is altered. 3 Enamel and skin apparently respond differently to heterozygous mutations affecting the α chain, because skin fragility was absent in carriers. In teeth, a single allele defect in the α chain in null mutation carriers is enough to disrupt ameloblast-coordinated replacement of basement membrane macromolecules causing enamel pitting.…”

Section: Discussionmentioning

confidence: 99%

“…2 Enamel in JEB is thin, hypoplastic and contains a 20% lower mineral content than that of healthy individuals. 3,4 Recently, we reported that heterozygous carriers of loss of function (null) mutations in LAMA3 exhibit dental abnormalities without skin symptoms. 5 Carriers exhibited localized enamel pitting and hypoplasia of secondary dentition.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

Gostyńska¹,

Yuen²,

Pasmooij³

et al. 2016

Eur J Hum Genet

View full text Add to dashboard Cite

The hereditary blistering disease junctional epidermolysis bullosa (JEB) is always accompanied by structural enamel abnormalities of primary and secondary dentition, characterized as amelogenesis imperfecta. Autosomal recessive mutations in LAMA3, LAMB3 and LAMC2 encoding the heterotrimer laminin 332 (LM-332) are among the genes causing JEB. While examining pedigrees of JEB patients with LAMA3 mutations, we observed that heterozygous carriers of functional null mutations displayed subtle enamel pitting in the absence of skin fragility or other JEB symptoms. Here, we report two new LAMA3 functional null mutations: nonsense c.2377C4T p.(Arg793Ter) and splice-site c.4684+1G4A mutation in heterozygous carriers exhibiting enamel pitting. Both parents had offspring affected with JEB and displayed subtle enamel pitting of secondary dentition without any sign of skin blistering. The reported enamel abnormality in LAMA3 mutation carriers could be attributed to a half dose effect of the laminin α3 chain (haploinsufficiency).

show abstract

Enamel Formation and Amelogenesis Imperfecta

Cited by 234 publications

References 128 publications

Amelogenin-Collagen Interactions Regulate Calcium Phosphate Mineralization in Vitro

Amelogenin-Collagen Interactions Regulate Calcium Phosphate Mineralization in Vitro

MicroRNA 224 Regulates Ion Transporter Expression in Ameloblasts To Coordinate Enamel Mineralization

Carriers with functional null mutations in LAMA3 have localized enamel abnormalities due to haploinsufficiency

Contact Info

Product

Resources

About