Smad3 is required for enamel biomineralization

Yokozeki, Masahiko; Afanador, Elaine; Nishi, Masumi; Kaneko, Kazuyuki; Shimokawa, Hitoyata; Yokote, Koutaro; Deng, Chu‐Xia; Tsuchida, Kunihiro; Sugino, Hiromu; Moriyama, Keiji

doi:10.1016/s0006-291x(03)00806-4

Cited by 31 publications

(26 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is suggested that when activated by TGF-β, SMAD proteins are critical for the regulation of dental development [Xu et al, 2003]. Preclinical studies in SMAD3-deficient mice have shown that, compared to their wild-type counterpart, molars and incisors in SMAD3-deficient mice exhibited a significant reduction in mineralization, suggesting that this protein is necessary for enamel biomineralization [Yokozeki et al, 2003]. Altogether, those data suggest that polymorphisms in the TGFBR1 gene may be associated DOI: 10.1159/000491644 with development of MIH by SMAD modulation, but additional functional studies may be able to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization

et al. 2018

View full text Add to dashboard Cite

Ameloblasts are sensitive cells whose metabolism and function may be affected by inflammatory stimuli. The aim of this study was to evaluate the possible association between polymorphisms in immune response-related genes and molar-incisor hypomineralization (MIH), and their interaction with polymorphisms in amelogenesis-related genes. DNA samples were obtained from 101 nuclear families that had at least 1 MIH-affected child. Eleven single-nucleotide polymorphisms (SNPs) were investigated in immune response genes using TaqMan® technology allele-specific probes. A transmission disequilibrium test was performed to verify overtransmission of alleles in all MIH families, as well as in families only with mild or severe MIH-affected children. Gene-gene interactions between the immune-related and amelogenesis-related polymorphisms were analyzed by determining whether alleles of those genes were transmitted from heterozygous parents more often in association than individually with MIH-affected children. In severe cases of MIH, significant results were observed for rs10733708 (TGFBR1, OR = 3.5, 95% CI = 1.1–10.6). Statistical evidence for gene-gene interactions between rs6654939 (AMELX) and the SNPs rs2070874 (IL4), rs2275913 (IL17A), rs1800872 (IL10), rs1800587 (IL1A), and rs3771300 (STAT1) was observed. The rs2070874 SNP (IL4) was also significantly overtransmitted from heterozygous parents with the rs7526319 (TUFT1) and the rs2355767 (BMP2) SNPs, suggesting a synergistic effect of the transmission of these alleles with susceptibility to MIH. This family-based study demonstrated an association between variation in TGFBR1 and MIH. Moreover, the polymorphisms in immune response and amelogenesis genes may have an additive effect on the risk of developing MIH.

show abstract

Section: Discussionmentioning

confidence: 99%

Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization

et al. 2018

View full text Add to dashboard Cite

show abstract

“…We also compared histology of enamel from Smad3 2/2 mice to that of Itgb6 2/2 , and they lacked similarity (unpublished results). Previous studies have also shown that ameloblast morphology remains unaltered in Smad3 2/2 mice although the enamel is poorly mineralized due to defective protein removal at the maturation stage (Yokozeki et al, 2003). Recently, it was reported that Smad3 and FoxO1 (transcriptional co-factor for Smads) collaboratively regulate genes involved in enamel formation (Poché et al, 2012).…”

Section: -Fold) In the Enamel Organs Of Itgb6mentioning

confidence: 99%

Critical role for αvβ6 integrin in enamel biomineralization

Mohazab

Koivisto

Jiang

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryTooth enamel has the highest degree of biomineralization of all vertebrate hard tissues. During the secretory stage of enamel formation, ameloblasts deposit an extracellular matrix that is in direct contact with the ameloblast plasma membrane. Although it is known that integrins mediate cell-matrix adhesion and regulate cell signaling in most cell types, the receptors that regulate ameloblast adhesion and matrix production are not well characterized. We hypothesized that avb6 integrin is expressed in ameloblasts where it regulates biomineralization of enamel. Human and mouse ameloblasts were found to express both b6 integrin mRNA and protein. The maxillary incisors of Itgb6 2/2 mice lacked yellow pigment and their mandibular incisors appeared chalky and rounded. Molars of Itgb6 2/2 mice showed signs of reduced mineralization and severe attrition. The mineral-to-protein ratio in the incisors was significantly reduced in Itgb6 2/2 enamel, mimicking hypomineralized amelogenesis imperfecta. Interestingly, amelogenin-rich extracellular matrix abnormally accumulated between the ameloblast layer of Itgb6 2/2 mouse incisors and the forming enamel surface, and also between ameloblasts. This accumulation was related to increased synthesis of amelogenin, rather than to reduced removal of the matrix proteins. This was confirmed in cultured ameloblast-like cells, in which avb6 integrin was not an endocytosis receptor for amelogenins, although it participated in cell adhesion on this matrix indirectly via endogenously produced matrix proteins. In summary, integrin avb6 is expressed by ameloblasts and it plays a crucial role in regulating amelogenin deposition and/or turnover and subsequent enamel biomineralization.

show abstract

“…Previously, the Smad3 transcriptional co-factor was implicated in the regulation of biomineralization in vivo , as mice with a targeted mutation in Smad3 exhibit a hypomineralized tooth phenotype [25], [26]. Given the well-documented role of Smad3 (together with the co-Smad, Smad4) as an intracellular molecule that mediates signaling from the Transforming growth factor-β (Tgf-β) receptor, we reasoned that Tgf-β signaling might activate a repertoire of genes necessary for the coordination of biomineralization [27].…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor FoxO1 Is Essential for Enamel Biomineralization

Poché

Sharma²,

Garcia

et al. 2012

PLoS ONE

View full text Add to dashboard Cite

The Transforming growth factor β (Tgf-β) pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-β signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta.

show abstract

Smad3 is required for enamel biomineralization

Cited by 31 publications

References 34 publications

Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization

Genes Regulating Immune Response and Amelogenesis Interact in Increasing the Susceptibility to Molar-Incisor Hypomineralization

Critical role for αvβ6 integrin in enamel biomineralization

Transcription Factor FoxO1 Is Essential for Enamel Biomineralization

Contact Info

Product

Resources

About