Cloning and Characterization of Porcine Enamelin mRNAs

Hu, C.-C.; Fukae, Makoto; Uchida, Takashi; Qin, Qian; Zhang, C.H.; Ryu, Ok Hee; Tanabe, T.; Yamakoshi, Yasuo; Murakami, Chikage; Dohi, Naofumi; Shimizu, Masaharu; Simmer, James P.

doi:10.1177/00220345970760110201

Cited by 139 publications

(117 citation statements)

References 33 publications

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“…Our observations further suggest that changes to highly conserved domains within enamel matrix proteins, such as amelogenin, can also alter enamel architecture and thickness. In addition, these observations provide a molecular basis for interpreting the changes in cell-matrix interactions that alter the shape and orientation of enamel rod and interrod that occurred during evolution of teeth and became preserved in the fossil record (21,69,70).…”

Section: Discussionmentioning

confidence: 95%

Altering Biomineralization by Protein Design

Zhu

Paine

Luo

et al. 2006

Journal of Biological Chemistry

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To create a bioceramic with unique materials properties, biomineralization exploits cells to create a tissue-specific protein matrix to control the crystal habit, timing, and position of the mineral phase. The biomineralized covering of vertebrate teeth is enamel, a distinctive tissue of ectodermal origin that is collagen-free. In forming enamel, amelogenin is the abundant protein that undergoes self-assembly to contribute to a matrix that guides its own replacement by mineral. Conserved domains in amelogenin suggest their importance to biomineralization. We used gene targeting in mice to replace native amelogenin with one of two engineered amelogenins. Replacement changed enamel organization by altering protein-to-crystallite interactions and crystallite stacking while diminishing the ability of the ameloblast to interact with the matrix. These data demonstrate that ameloblasts must continuously interact with the developing matrix to provide amelogenin-specific protein to protein, protein to mineral, and protein to membrane interactions critical to biomineralization and enamel architecture while suggesting that mutations within conserved amelogenin domains could account for enamel variations preserved in the fossil record.In mammals mesenchyme-derived bone is the dominant biomineralized tissue and is composed of substituted hydroxyapatite crystals with specific proteins distributed in an abundant collagen network (1-3). For bone, the mineral composite is dynamic with both the protein and mineral phases being constantly remodeled by cells. A notable exception to such a biomineralization theme is found in enamel, the vertebrate covering of teeth. In teeth, ectoderm-derived ameloblasts synthesize a short-lived, diverse repertoire of proteins that self-assemble to produce a matrix that directs its own replacement by the mineral phase (4, 5). Mature enamel is a bioceramic composed of less than 0.5% protein that is dispersed among the longest hydroxyapatite crystals in the vertebrate body (6 -8). Unlike mesenchyme-derived bone, enamel does not contain collagen, does not have the capacity of self-repair, and does not undergo remodeling. Nonetheless, enamel lasts the lifetime of the organism due its unique material properties and remarkable resistance to failure (9, 10). These properties are due in part to the cell-directed organization of crystallites into bundles called rods. Rods are further woven together during their formation by cell migration to form a unique three-dimensional lattice architecture that resists wear and deformation (9 -14).Amelogenin is the most abundant of the enamel matrix proteins and undergoes self-assembly to form nanospheres (15-17). Amelogenin nanospheres appear to control the habit of hydroxyapatite crystallites by directing mineral growth to the ends (cЈ axis) of the crystallites by providing the space for crystallites to grow within and by buffering the local environment against protons liberated during mineral deposition (5, 7, 18 -20). The amino acid sequence of amelogenin is highly ...

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Section: Discussionmentioning

confidence: 95%

Altering Biomineralization by Protein Design

Zhu

Paine

Luo

et al. 2006

Journal of Biological Chemistry

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“…During the secretory stage, ameloblasts secrete mostly amelogenin, enamelin and ameloblastin (Hu et al, 1997a;Hu et al, 1997b;Krebsbach et al, 1996;Snead et al, 1985). These proteins catalyze the extension of ribbon-like enamel crystallites comprised of the mineral calcium hydroxyapatite.…”

Section: Dental Enamel Formationmentioning

confidence: 99%

Functions of KLK4 and MMP-20 in dental enamel formation

Papagerakis²,

Yamakoshi

et al. 2008

BCHM

219

190

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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.

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“…The major secretory stage enamel proteins are amelogenin (21,22), ameloblastin (23)(24)(25), and enamelin (26,27). These proteins function specifically during enamel formation, and the disease phenotypes exhibited by mice lacking these genes are confined to the developing teeth and include enamel agenesis (28 -30).…”

mentioning

confidence: 99%

Hypomaturation Enamel Defects in Klk4 Knockout/LacZ Knockin Mice

Simmer

Lertlam

et al. 2009

Journal of Biological Chemistry

134

184

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Kallikrein 4 (Klk4) is believed to play an essential role in enamel biomineralization, because defects in KLK4 cause hypomaturation amelogenesis imperfecta. We used gene targeting to generate a knockin mouse that replaces the Klk4 gene sequence, starting at the translation initiation site, with a lacZ reporter gene. Correct targeting of the transgene was confirmed by Southern blot and PCR analyses. Histochemical X-gal (5-bromo-4-chloro-3-indolyl-␤-D-galactopyranoside) staining demonstrated expression of ␤-galactosidase in maturation stage ameloblasts. No X-gal staining was observed in secretory stage ameloblasts or in odontoblasts. Retained enamel proteins were observed in the maturation stage enamel of the Klk4 null mouse, but not in the Klk4 heterozygous or wild-type mice. The enamel layer in the Klk4 null mouse was normal in thickness and contained decussating enamel rods but was rapidly abraded following weaning, despite the mice being maintained on soft chow. In function the enamel readily fractured within the initial rod and interrod enamel above the parallel enamel covering the dentinoenamel junction. Despite the lack of Klk4 and the retention of enamel proteins, significant levels of crystal maturation occurred (although delayed), and the enamel achieved a mineral density in some places greater than that detected in bone and dentin. An important finding was that individual enamel crystallites of erupted teeth failed to grow together, interlock, and function as a unit. Instead, individual crystallites seemed to spill out of the enamel when fractured. These results demonstrate that Klk4 is essential for the removal of enamel proteins and the proper maturation of enamel crystals.Dental enamel is composed of highly ordered, very long crystals of calcium hydroxyapatite (Ca 10 (PO 4 ) 6 (OH) 2 ). Mature enamel crystallites are about 70 nm wide and 30 nm thick, but are of unmeasurable length (1), probably extending all the way from the dentin layer to the surface of the tooth (2). Enamel crystallites are organized into bundles called rods, with about 10,000 parallel crystals in a rod (3). Each enamel rod is the product of a single ameloblast, the cell type that forms a continuous sheet over the developing enamel and orchestrates its formation. Dental enamel of erupted teeth is ϳ95% mineral (by weight) (4), with most of the non-mineral component being water. Protein comprises Ͻ1% of its weight. Forming enamel, however, is over 30% protein (5). Much of the protein is reabsorbed by ameloblasts and degraded in lysosomes (6, 7), but extracellular proteases also play a role in matrix protein removal (8 -10).Dental enamel formation is divided into secretory, transition, and maturation stages (11,12). During the secretory stage, enamel crystals grow primarily in length. As the crystals extend, the enamel layer expands. Enamel crystallites lengthen along a mineralization front at the secretory surface of the ameloblast cell membrane. There, mineral deposits rapidly on the crystallite tips, and very slowly on their sides...

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Cloning and Characterization of Porcine Enamelin mRNAs

Cited by 139 publications

References 33 publications

Altering Biomineralization by Protein Design

Altering Biomineralization by Protein Design

Functions of KLK4 and MMP-20 in dental enamel formation

Hypomaturation Enamel Defects in Klk4 Knockout/LacZ Knockin Mice

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