Evidence for Amelogenin "Nanospheres" as Functional Components of Secretory-Stage Enamel Matrix

Fincham, Alan G.; Moradian‐Oldak, Janet; Diekwisch, Thomas G.H.; Lyaruu, D.M.; Wright, J. Timothy; Bringas, Pablo; Slavkin, Harold C.

doi:10.1006/jsbi.1995.1029

Cited by 275 publications

(273 citation statements)

References 0 publications

Supporting

Mentioning

253

Contrasting

Unclassified

Order By: Relevance

“…1 B and H, and Fig. S3 A-D), which were identified as amelogenin nanospheres (12)(13)(14). A few short chains of the nanospheres were also observed at this stage ( Fig.…”

Section: Resultsmentioning

confidence: 79%

“…The TRAP and C-telopeptide domains are involved in molecular recognition between amelogenin molecules, which is essential for proper enamel formation (7). Amelogenin self-assembles at pH values above 6.5 forming nanospheres, spherical (12,13) or oblate (14) structures 10-20 nm in diameter, which are believed to play a key role in the mineralization and structural organization of enamel. When secreted, amelogenin undergoes a series of proteolytic cleavages starting at the C telopeptide (15).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Hierarchical self-assembly of amelogenin and the regulation of biomineralization at the nanoscale

Fang

Conway

Margolis³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

173

184

View full text Add to dashboard Cite

Enamel is a highly organized hierarchical nanocomposite, which consists of parallel arrays of elongated apatitic crystallites forming an intricate three-dimensional microstructure. Amelogenin, the major extracellular matrix protein of dental enamel, regulates the formation of these crystalline arrays via cooperative interactions with forming mineral phase. Using cryoelectron microscopy, we demonstrate that amelogenin undergoes stepwise hierarchical self-assembly. Furthermore, our results indicate that interactions between amelogenin hydrophilic C-terminal telopeptides are essential for oligomer formation and for subsequent steps of hierarchical self-assembly. We further show that amelogenin assemblies stabilize mineral prenucleation clusters and guide their arrangement into linear chains that organize as parallel arrays. The prenucleation clusters subsequently fuse together to form needle-shaped mineral particles, leading to the formation of bundles of crystallites, the hallmark structural organization of the forming enamel at the nanoscale. These findings provide unique insight into the regulation of biological mineralization by specialized macromolecules and an inspiration for bottom-up strategies for the materials design.

show abstract

“…1 B and H, and Fig. S3 A-D), which were identified as amelogenin nanospheres (12)(13)(14). A few short chains of the nanospheres were also observed at this stage ( Fig.…”

Section: Resultsmentioning

confidence: 79%

mentioning

confidence: 99%

Hierarchical self-assembly of amelogenin and the regulation of biomineralization at the nanoscale

Fang

Conway

Margolis³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

173

184

View full text Add to dashboard Cite

show abstract

“…Amelogenins are thought to self-aggregate as shown in several in vitro studies (33)(34)(35). Amelogenin self-assembly in vitro resulted in the formation of structures referred to as nanospheres that were proposed as the functional components of secretory stage enamel (33).…”

Section: Discussionmentioning

confidence: 99%

“…Amelogenin self-assembly in vitro resulted in the formation of structures referred to as nanospheres that were proposed as the functional components of secretory stage enamel (33). This model suggested that the N-terminal domain of amelogenin is involved with the formation of nanospheres, whereas the C-terminal region contributes to stability and homogeneity in size of nanospheres, preventing mineral crystal fusion to form larger structures prematurely (36).…”

Section: Discussionmentioning

confidence: 99%

Amelogenin-deficient Mice Display an Amelogenesis Imperfecta Phenotype

Gibson

Yuan

Hall

et al. 2001

Journal of Biological Chemistry

429

448

View full text Add to dashboard Cite

Dental enamel is the hardest tissue in the body and cannot be replaced or repaired, because the enamel secreting cells are lost at tooth eruption. X-linked amelogenesis imperfecta (MIM 301200), a phenotypically diverse hereditary disorder affecting enamel development, is caused by deletions or point mutations in the human Xchromosomal amelogenin gene. Although the precise functions of the amelogenin proteins in enamel formation are not well defined, these proteins constitute 90% of the enamel organic matrix. We have disrupted the amelogenin locus to generate amelogenin null mice, which display distinctly abnormal teeth as early as 2 weeks of age with chalky-white discoloration. Microradiography revealed broken tips of incisors and molars and scanning electron microscopy analysis indicated disorganized hypoplastic enamel. The amelogenin null phenotype reveals that the amelogenins are apparently not required for initiation of mineral crystal formation but rather for the organization of crystal pattern and regulation of enamel thickness. These null mice will be useful for understanding the functions of amelogenin proteins during enamel formation and for developing therapeutic approaches for treating this developmental defect that affects the enamel.

show abstract

“…These proteins catalyze the extension of ribbon-like enamel crystallites comprised of the mineral calcium hydroxyapatite. Amelogenin is the predominant secretory product of ameloblasts and assembles into spheres that occupy the spaces between the crystal ribbons, serving to separate and support them Fincham et al, 1995). Ameloblasts must retreat away from the expanding enamel surface as they secrete enamel proteins.…”

Section: Dental Enamel Formationmentioning

confidence: 99%

Functions of KLK4 and MMP-20 in dental enamel formation

Papagerakis²,

Yamakoshi

et al. 2008

BCHM

219

190

View full text Add to dashboard Cite

Two proteases are secreted into the enamel matrix of developing teeth. The early protease is enamelysin . The late protease is kallikrein 4 (KLK4). Mutations in MMP20 and KLK4 both cause autosomal recessive amelogenesis imperfecta, a condition featuring soft, porous enamel containing residual protein. MMP-20 is secreted along with enamel proteins by secretory stage ameloblasts. Enamel protein cleavage products accumulate in the space between the crystal ribbons, helping to support them. MMP-20 steadily cleaves accumulated enamel proteins, so their concentration decreases with depth. Kallikrein 4 is secreted by transition and maturation stage ameloblasts. KLK4 aggressively degrades the retained organic matrix following the termination of enamel protein secretion. The principle functions of MMP-20 and KLK4 in dental enamel formation are to facilitate the orderly replacement of organic matrix with mineral, generating an enamel layer that is harder, less porous, and unstained by retained enamel proteins.

show abstract

Evidence for Amelogenin "Nanospheres" as Functional Components of Secretory-Stage Enamel Matrix

Cited by 275 publications

References 0 publications

Hierarchical self-assembly of amelogenin and the regulation of biomineralization at the nanoscale

Hierarchical self-assembly of amelogenin and the regulation of biomineralization at the nanoscale

Amelogenin-deficient Mice Display an Amelogenesis Imperfecta Phenotype

Functions of KLK4 and MMP-20 in dental enamel formation

Contact Info

Product

Resources

About