Partial Rescue of the Amelogenin Null Dental Enamel Phenotype

Li, Yong; Suggs, C.; Wright, J. Timothy; Yuan, Zhenhua; Aragon, Melissa; Fong, Hanson; Simmons, Darrin; Daly, Bill; Golub, Ellis E.; Harrison, Greg J.; Kulkarni, Ashok B.; Gibson, Carolyn W.

doi:10.1074/jbc.m707992200

Cited by 29 publications

(54 citation statements)

References 52 publications

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“…Studies in amelogenin knockout mice showed that amelogenin plays an important role in enamel biomineralization (6,7), and while ameloblast differentiation is relatively normal in these mice, an abnormally thin enamel layer is formed (8). Amelogenins are essential for the formation of hydroxyapatite in enamel (9), and they are also recognized as a key factor in controlling the orientation and elongated growth of enamel rods during the mineralization process (10). In addition to amelogenin, the developing enamel is composed of several structural proteins such as ameloblastin (sheathlin/amelin), enamelin, and tuftelin.…”

Section: Enamelmentioning

confidence: 99%

Enamel Tissue Engineering

Honda¹,

Hata²

2010

Tissue Engineering

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Section: Enamelmentioning

confidence: 99%

Enamel Tissue Engineering

Honda¹,

Hata²

2010

Tissue Engineering

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“…AmelxKO and Mmp20KO mice were generated by introduction of a deletion into the coding region as described previously (Gibson et al, 2001;Caterina et al, 2002). The C-terminus truncated (CTRNCTg) and M180 transgenic mice were generated as previously described (Pugach et al, 2010;Li et al, 2008). To determine the genotype of AmelxKO, Mmp20KO, and transgene-positive offspring, we isolated high-molecular-weight genomic DNA from mouse tails (Chen et al, 2003).…”

Section: Materials and Methods Transgenic And Knockout Micementioning

confidence: 99%

“…To determine the genotype of AmelxKO, Mmp20KO, and transgene-positive offspring, we isolated high-molecular-weight genomic DNA from mouse tails (Chen et al, 2003). The amelogenin, Mmp20, CTRNCTg, and M180Tg PCR primers and conditions used have been described (Caterina et al, 2002;Li et al, 2008;Pugach et al, 2010).…”

Section: Materials and Methods Transgenic And Knockout Micementioning

confidence: 99%

“…Mandibles were dissected from mouse heads as described (Li et al, 2008). Elastic modulus and hardness of molar enamel were determined in adult (6 wks and 3 mos old) mice (n = 6) by a Nanoindenter XP (MTS Systems, Oak Ridge, TN, USA).…”

Section: Nanomechanical Property Measurements Of Teethmentioning

confidence: 99%

“…These defects can be partially rescued by mating the AmelxKO mice with mice expressing an amelogenin transgene (M180) (Li et al, 2008). M180 is the most abundant splice variant in mice, consisting of 180 amino acids, 13 of which are normally cleaved from the C-terminus by Mmp20 immediately after secretion.…”

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confidence: 99%

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M180 Amelogenin Processed by MMP20 is Sufficient for Decussating Murine Enamel

Pugach

Suggs

et al. 2013

J Dent Res

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Amelogenin (AMELX) and matrix metalloproteinase-20 (MMP20) are essential for proper enamel development. Amelx and Mmp20 mutations cause amelogenesis imperfecta. MMP20, a protease secreted by ameloblasts, is responsible for processing enamel proteins, including AMELX, during the secretory stage of enamel formation. Of at least 16 different amelogenin splice products, the most abundant isoform found in murine ameloblasts and developing enamel is the M180 protein. To understand the role of MMP20 processing of M180 AMELX, we generated AmelxKO/Mmp20KO (DKO) mice with an amelogenin (M180Tg) transgene. We analyzed the enamel phenotype by SEM to determine enamel structure and thickness, µCT, and by nanoindentation to quantify enamel mechanical properties. M180Tg/DKO mouse enamel had 37% of the hardness of M180Tg/AmelxKO teeth and demonstrated a complete lack of normal prismatic architecture. Although molar enamel of M180Tg/AmelxKO mice was thinner than WT, it had similar mechanical properties and decussating enamel prisms, which were abolished by the loss of MMP20 in the M180Tg/DKO mice. Retention of the C-terminus or complete lack of this domain is unable to rescue amelogenin null enamel. We conclude that among amelogenins, M180 alone is sufficient for normal enamel mechanical properties and prism patterns, but that additional amelogenin splice products are required to restore enamel thickness.

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Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

Suzuki

Haruyama

Nishimura

et al. 2012

Archives of Oral Biology

Self Cite

134

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Dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) are highly phosphorylated proteins that belong to the family of small integrin-binding ligand N-linked glycoproteins (SIBLINGs), and are essential for proper development of hard tissues such as teeth and bones. In order to understand how they contribute to tissue organization, DSPP and DMP-1 have been analyzed for over a decade using both in vivo and in vitro techniques. Among the five SIBLINGs, the DSPP and DMP-1 genes are located next to each other and their gene and protein structures are most similar. In this review we examine the phenotypes of the genetically engineered mouse models of DSPP and DMP-1 and also introduce complementary in vitro studies into the molecular mechanisms underlying these phenotypes. DSPP affects the mineralization of dentin more profoundly than DMP-1. In contrast, DMP-1 significantly affects bone mineralization and importantly controls serum phosphate levels by regulating serum FGF-23 levels, whereas DSPP does not show any systemic effects. DMP-1 activates integrin signaling and is endocytosed into the cytoplasm whereupon it is translocated to the nucleus. In contrast, DSPP only activates integrin-dependent signaling. Thus it is now clear that both DSPP and DMP-1 contribute to hard tissue mineralization and the tissues affected by each are different presumably as a result of their different expression levels. In fact, in comparison with DMP-1, the functional analysis of cell signaling by DSPP remains relatively unexplored.

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Partial Rescue of the Amelogenin Null Dental Enamel Phenotype

Cited by 29 publications

References 52 publications

Enamel Tissue Engineering

Enamel Tissue Engineering

M180 Amelogenin Processed by MMP20 is Sufficient for Decussating Murine Enamel

Dentin sialophosphoprotein and dentin matrix protein-1: Two highly phosphorylated proteins in mineralized tissues

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