p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion

Greenblatt, Matthew B.; Kim, Jung-Min; Oh, Han; Park, Kwang Hwan; Choo, Min‐Kyung; Sano, Yasuyo; Tye, Coralee E.; Skobe, Ziedonis; Davis, Roger J.; Park, Jin Mo; Bei, Marianna; Glimcher, Laurie H.; Shim, Jae-Hyuck

doi:10.1074/jbc.m114.599274

Cited by 27 publications

(23 citation statements)

References 36 publications

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“…In addition, it has been reported that the P38 MAPK pathway is required for the effects of BMP2 and BMP7 on tooth development, such as the expression of p21 in the embryonic enamel knot and the expression of enamelin, ameloblastin, and β4-integrin in ameloblasts; mice with a deletion of P38 in the ectoderm display defective secretion of dental enamel and the absence of dental cusps. 24 ERK 1/2 MAPK has been reported to play an important role in TGF-β1-induced growth, collagen turnover, and differentiation of stem cells from tooth apical papilla. 25 Therefore, further study is needed to identify the involvement of the P38 and ERK1/2 pathways in the regulation of ameloblastic differentiation of iPS cells induced by growth factors within the ameloblast-conditioned medium, such as BMP2, BMP7, and TGF-β1.…”

Section: Discussionmentioning

confidence: 99%

Smad1/5 signal transduction regulates the ameloblastic differentiation of induced pluripotent stem cells

Zeng

Qin

et al. 2020

Braz. oral res.

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Induced pluripotent stem (iPS) cells could be induced into ameloblast-like cells by ameloblasts serum-free conditioned medium (ASF-CM), and bone morphogenetic proteins (BMPs) might be essential during the regulation of this process. The present study investigates the signal transduction that regulates the ameloblastic differentiation of iPS cells induced by ASF-CM. Mouse iPS cells were characterized and then cultured for 14 days in epithelial cell medium (control) or ASF-CM. Bone morphogenetic protein receptor II (BMPR-II) siRNA, inhibitor of Smad1/5 phosphorylation activated by activin receptor-like kinase (ALK) receptors, and inhibitors of mitogen-activated protein kinases (MAPKs) phosphorylation were used to treat the iPS cells in combination with ASF-CM. Real-time PCR, western blotting, and immunofluorescent staining were used to evaluate the expressions of ameloblast markers ameloblastin, enamelin, and cytokeratin-14. BMPR-II gene and protein levels increased markedly in ASF-CMtreated iPS cells compared with the controls, while the mRNA levels of Bmpr-Ia and Bmpr-Ib were similar between the ASF-CM and control groups. ASF-CM stimulation significantly increased the gene and protein expression of ameloblastin, enamelin and cytokeratin-14, and phosphorylated SMAD1/5, p38 MAPK, and ERK1/2 MAPK compared with the controls. Knockdown of BMPR-II and inhibition of Smad1/5 phosphorylation both could significantly reverse the increased expression of ameloblastin, enamelin, and cytokeratin-14 induced by ASF-CM, while neither inhibition of p38 nor ERK1/2 phosphorylation had significant reversing effects. We conclude that smad1/5 signaling transduction, activated by ALK receptors, regulates the ameloblastic differentiation of iPS cells induced by ameloblast-conditioned medium.

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Section: Discussionmentioning

confidence: 99%

Smad1/5 signal transduction regulates the ameloblastic differentiation of induced pluripotent stem cells

Zeng

Qin

et al. 2020

Braz. oral res.

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“…Jernvall J, et al, determine that the role of mesenchymal Bmp-4 is the stimulation of p21 expression in enamel knot at early cap stage ceasiting the proliferation in enamel knot [51]. p38α MAPK pathway also controls p21 expression in response to BMP2/7 [52]. BMP-4 is necessary for expression of Zeb1 and Zeb2 in the enamel knot too [53].…”

Section: Primary Enamel Knot (Pek)mentioning

confidence: 99%

“…Amelogenesis: Similar to dentinogenesis, in amelogenesis many different factors have also effects on enamel secretion and/or mineralization, thus we design again a Table where the factors are classified according to its role in secretion and/or mineralization (Table 4) [50,52,67,77,83,98,100,103,119,126,[128][129][130][131][132][133][134].…”

Section: Dentinogenesismentioning

confidence: 99%

“…Other studies have related Sp6 to amelogenesis via down-regulation of follistatin gene expression [135], which may function in BMPs antagonism in ameloblast [110,135,136]. RhoA-MKK6-p38α signaling axis is crucial for enamel secretion since they induce p21, amelogenin and ameloblastin genes and p21 transcriptional activation by BMP-2/7 [52].…”

Section: Secretion Mineralizationmentioning

confidence: 99%

“…In Table 5 [52,69,104,111,126,128,[131][132][133][137][138][139][140][141] we related factors to different proteins and genes of enamel formation. For example, C/EBP-α and YY1 interact co-operatively which seem to contribute to the down-modulation of amelogenin gene expression [141].…”

Section: Secretion Mineralizationmentioning

confidence: 99%

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Growth and Transcription Factors in Tooth Development

Sousa-Romero¹

2016

Int J Oral Craniofac Sci

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Odontogenesis is a complex embryonic process originated by the interaction between two main embryonic components, dental epithelium and ectomesenchyme. This ectomesenchymal interaction is mediated by growth and transcription factors controlling the different aspects of tooth development such as tooth initiation, enamel knot formation and/or cell proliferation and differentiation. The aim of this review was to establish which factors are, how they interact and their functions in Odontogenesis. We have described several signaling pathways which are essential for correct tooth development and organized all available information. Our conclusion is that instead of large amount of information about tooth development, further studies are necessary to clear several essential mechanisms which still remain unknown and/or unclear. Thickening of dental epithelium and mesenchymal condensation: Epithelial BMP-4 and FGF-8 are essential in control of target genes transcription at this stage. They interact, BMP-4 as inhibitor and FGF-8 as inducer, and lead to different responses (Figure 2) [7,16,19] controlling epithelial proliferation. Early markers of tooth position and tooth type: Prior to thickening of dental epithelium various factors are expressed in dental epithelium and mesenchyme determining the position and pattern of prospective tooth.

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MiR-1a-3p Inhibits Apoptosis in Fluoride-exposed LS8 Cells by Targeting Map3k1

Chen,

Gu,

Bai

et al. 2023

Biol Trace Elem Res

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Dental fluorosis is a common chemical disease. It is currently unclear how fluorosis occurs at the molecular level. We used miRNA-seq to look at the differences between miRNAs in the cell line of ameloblasts LS8 that had been treated with 3.2 mmol/L NaF. We also performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. miR-1a-3p levels were significantly lower in mouse LS8 cells treated with 3.2 mmol/L NaF, and miR-1a-3p-targeted genes were significantly enriched in the MAPK pathway. LS8 cells were divided into four groups: control, NaF, NaF+miR-1a-3p mimics, and NaF+miR-1a-3p mimics normal control groups. Cellular morphology was observed by an inverted microscope, and the proliferation activity of LS8 cells was assessed by Cell Counting Kit-8 (CCK-8). Using the real-time quantitative polymerase chain reaction (RT-qPCR), transcription levels of miR-1a-3p and Map3k1 were detected. The expressions of Bax, Bcl-2, Map3k1, p38MAPK, ERK1/2, p-p38MAPK, and p-ERK1/2 were measured by Western blot. After bioinformatics analysis, we used a luciferase reporter assay (LRA) to validate the target of miR-1a-3p, showing that miR-1a-3p could inhibit apoptosis while increasing proliferation in fluoride-exposed LS8 cells. Generally, miR-1a-3p might directly inhibit Map3k1, reduce MAPK signal pathway activation, and promote phosphorylation. Thus, our findings revealed that the interaction of miR-1a-3p with its target gene Map3k1 and MAPK signal pathway might decrease the apoptosis of LS8 cells treated with 3.2 mmol/L NaF.

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p38α MAPK Is Required for Tooth Morphogenesis and Enamel Secretion

Cited by 27 publications

References 36 publications

Smad1/5 signal transduction regulates the ameloblastic differentiation of induced pluripotent stem cells

Smad1/5 signal transduction regulates the ameloblastic differentiation of induced pluripotent stem cells

Growth and Transcription Factors in Tooth Development

MiR-1a-3p Inhibits Apoptosis in Fluoride-exposed LS8 Cells by Targeting Map3k1

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