Apoptosis in the reduced enamel epithelium just after tooth emergence in rats

Abiko, Yoshihiro; Nishimura, Michiko; Arai, Jiro; Kuraguchi, Jun; Saitoh, Masato; Kaku, Tohru

doi:10.1007/bf02349044

Cited by 11 publications

(4 citation statements)

References 5 publications

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“…4H ). To further confirm the rapid ameloblastic differentiation of hKSCs in chimeric tooth germs, we further performed immunohistochemistry and TUNEL assays to examine the expression profiles of amelogenin and ameloblastin, two molecular markers for differentiating ameloblasts [ 40 , 41 ], and the programmed cell death at various time points [ 42 ]. Strikingly, we found that expression of amelogenin and ameloblastin was not detectable in the hKSC-derived dental epithelia in the recombinants at day 8 (Fig.…”

Section: Resultsmentioning

confidence: 99%

Efficient induction of functional ameloblasts from human keratinocyte stem cells

Lee

Zheng

et al. 2018

Stem Cell Res Ther

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BackgroundAlthough adult human tissue-derived epidermal stem cells are capable of differentiating into enamel-secreting ameloblasts and forming teeth with regenerated enamel when recombined with mouse dental mesenchyme that possesses odontogenic potential, the induction rate is relatively low. In addition, whether the regenerated enamel retains a running pattern of prism identical to and acquires mechanical properties comparable with human enamel indeed warrants further study.MethodsCultured human keratinocyte stem cells (hKSCs) were treated with fibroblast growth factor 8 (FGF8) and Sonic hedgehog (SHH) for 18 h or 36 h prior to being recombined with E13.5 mouse dental mesenchyme with implantation of FGF8 and SHH-soaked agarose beads into reconstructed chimeric tooth germs. Recombinant tooth germs were subjected to kidney capsule culture in nude mice. Harvested samples at various time points were processed for histological, immunohistochemical, TUNEL, and western blot analysis. Scanning electronic microscopy and a nanoindentation test were further employed to analyze the prism running pattern and mechanical properties of the regenerated enamel.ResultsTreatment of hKSCs with both FGF8 and SHH prior to tissue recombination greatly enhanced the rate of tooth-like structure formation to about 70%. FGF8 and SHH dramatically enhanced stemness of cultured hKSCs. Scanning electron microscopic analysis revealed the running pattern of intact prisms of regenerated enamel is similar to that of human enamel. The nanoindentation test indicated that, although much softer than human child and adult mouse enamel, mechanical properties of the regenerated enamel improved as the culture time was extended.ConclusionsApplication of FGF8 and SHH proteins in cultured hKSCs improves stemness but does not facilitate odontogenic fate of hKSCs, resulting in an enhanced efficiency of ameloblastic differentiation of hKSCs and tooth formation in human–mouse chimeric tooth germs.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-0822-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Efficient induction of functional ameloblasts from human keratinocyte stem cells

Lee

Zheng

et al. 2018

Stem Cell Res Ther

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“…Tooth development undergoes various stages, with the formation of tooth crown through the differentiation of dentin-secreting odontoblasts and enamel-producing ameloblasts. Ameloblasts are lost via their transformation and apoptosis upon tooth eruption (Abiko et al, 1996), making it impossible to repair or replace lost/damaged enamel in erupted teeth.…”

Section: Introductionmentioning

confidence: 99%

Induction of human keratinocytes into enamel-secreting ameloblasts

Wang

Liu

et al. 2010

Developmental Biology

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Mammalian tooth development relies heavily on the reciprocal and sequential interactions between cranial neural crest-derived mesenchymal cells and stomadial epithelium. During mouse tooth development, odontogenic potential, that is, the capability to direct an adjacent tissue to form a tooth, resides in dental epithelium initially, and shifts subsequently to dental mesenchyme. Recent studies have shown that mouse embryonic dental epithelium possessing odontogenic potential is able to induce the formation of a bioengineered tooth crown when confronted with postnatal mesenchymal stem cells of various sources. Despite many attempts, however, postnatal stem cells have not been used successfully as the epithelial component in the generation of a bioengineered tooth. We show here that epithelial sheets of cultured human keratinocytes, when recombined with mouse embryonic dental mesenchyme, are able to support tooth formation. Most significantly, human keratinocytes, recombined with mouse embryonic dental mesenchyme in the presence of exogenous FGF8, are induced to express the dental epithelial marker PITX2 and differentiate into enamel-secreting ameloblasts that develop a human-mouse chimeric whole tooth crown. We conclude that in the presence of appropriate odontogenic signals, human keratinocytes can be induced to become odontogenic competent; and that these are capable of participating in tooth crown morphogenesis and differentiating into ameloblasts. Our studies identify human keratinocytes as a potential cell source for in vitro generation of bioengineered teeth that may be used in replacement therapy.

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“…The significant increase in the active transport of mineral ions into the matrix during this stage accelerates enamel crystal growth in both width and thickness until the tissue volume is eventually occluded by mineral (6). Finally, the ameloblasts reduce, undergo apoptosis and on tooth eruption, are completely lost (7). …”

Section: Introductionmentioning

confidence: 99%

Deletion of amelotin exons 3–6 is associated with amelogenesis imperfecta

et al. 2016

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Amelogenesis imperfecta (AI) is a heterogeneous group of genetic conditions that result in defective dental enamel formation. Amelotin (AMTN) is a secreted protein thought to act as a promoter of matrix mineralization in the final stage of enamel development, and is strongly expressed, almost exclusively, in maturation stage ameloblasts. Amtn overexpression and Amtn knockout mouse models have defective enamel with no other associated phenotypes, highlighting AMTN as an excellent candidate gene for human AI. However, no AMTN mutations have yet been associated with human AI. Using whole exome sequencing, we identified an 8,678 bp heterozygous genomic deletion encompassing exons 3-6 of AMTN in a Costa Rican family segregating dominant hypomineralised AI. The deletion corresponds to an in-frame deletion of 92 amino acids, shortening the protein from 209 to 117 residues. Exfoliated primary teeth from an affected family member had enamel that was of a lower mineral density compared to control enamel and exhibited structural defects at least some of which appeared to be associated with organic material as evidenced using elemental analysis. This study demonstrates for the first time that AMTN mutations cause non-syndromic human AI and explores the human phenotype, comparing it with that of mice with disrupted Amtn function.

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Apoptosis in the reduced enamel epithelium just after tooth emergence in rats

Cited by 11 publications

References 5 publications

Efficient induction of functional ameloblasts from human keratinocyte stem cells

Efficient induction of functional ameloblasts from human keratinocyte stem cells

Induction of human keratinocytes into enamel-secreting ameloblasts

Deletion of amelotin exons 3–6 is associated with amelogenesis imperfecta

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