Smad4-Shh-Nfic signaling cascade–mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development

Huang, Xiaofeng; Xu, Xun; Bringas, Pablo; Hung, Yee Ping; Chai, Yang

doi:10.1359/jbmr.091103

Cited by 140 publications

(188 citation statements)

References 49 publications

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“…In particular, the coordinated development of odontoblast cells depends on the adjustment of various regulators that are responsible for the induction of cell differentiation and the expression of tooth-specific genes. Previous studies have shown that dentinogenesis, a complex process in which multiple signaling pathways induce dentin formation, is controlled by many growth and transcription factors (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). However, the regulation of DSPP is not fully understood, particularly the understanding of its post-transcriptional regulation.…”

Section: Introductionmentioning

confidence: 99%

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

Huang

Xu²,

Gao³

et al. 2011

Int J Mol Med

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Abstract. Dentin sialophosphoprotein (DSPP), an important marker of odontoblast differentiation, is a prerequisite for tooth development and mineralization; however, the molecular mechanisms of both temporal and spatial regulation remain unknown. MicroRNAs (miRNAs) provide an additional level of control beyond that of transcription factors, which regulate post-transcriptional control of gene expression. The present study was designed to provide a first attempt at an in-depth analysis of dental pulp cells at various odontoblastic differentiation stages to obtain miRNA differential expression patterns, and to determine the contribution of miRNAs in the expression of DSPP during odontoblast differentiation. Dual luciferase reporter assays and qRT-PCR were used to validate miRNAs identified from bioinformatic analyses to determine whether they were able to regulate the DSPP gene in dental pulp cells cultured in a mineralizing medium. The results presented here suggest that DSPP is regulated post-transcriptionally by mir32, mir885-5p and mir586 during odontoblast differentiation.

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Section: Introductionmentioning

confidence: 99%

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

Huang

Xu²,

Gao³

et al. 2011

Int J Mol Med

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“…Interestingly, mice with conditional deletion of both TGF-β/BMP signaling in odontoblasts (OC-Cre;Smad4 fl/fl ) resulted in a high rate of keratocystic odontogenic tumors in the jaw (11). Furthermore, K14-Cre;Smad4 fl/fl mice exhibited arrest of root formation; HERS was elongated, but not fragmented (9). Taken together, TGF-β signaling appears to play a central role in both of dental mesenchyme and epithelium during tooth root development.…”

mentioning

confidence: 99%

<b>Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by </b><b>TGF-β </b>

et al. 2017

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In tooth root development, periodontal ligament (PDL) and cementum are formed by the coordination with the fragmentation of Hertwig's epithelial root sheath (HERS) and the differentiation of dental follicle mesenchymal cells. However, the function of the dental epithelial cells after HERS fragmentation in the PDL is not fully understood. Here, we found that TGF-β regulated HERS fragmentation via epithelial-mesenchymal transition (EMT), and the fragmented epithelial cells differentiated into PDL fibroblastic cells with expressing of PDL extracellular matrix (ECM). In the histochemical analysis, TGF-β was expressed in odontoblast layer adjacent of HERS during root development. Periostin expression was detected around fragmented epithelial cells on the root surface, but not in HERS. In the experiment using an established mouse HERS cell line (HERS01a), TGF-β1 treatment decreased E-cadherin and relatively increased N-cadherin expression. TGF-β1 treatment in HERS01a induced further expression of important ECM proteins for acellular cementum and PDL development such as fibronectin and periostin. Taken together, activation of TGF-β signaling induces HERS fragmentation through EMT and the fragmented HERS cells contribute to formation of PDL and acellular cementum through periostin and fibronectin expression.

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“…Recently, Shh signaling is specifically expressed in Hertwig's epithelial root sheath in mice and plays an important role in the formation of molar tooth 22) . Shh depends on Smad4 signaling to induce Nfic which controls TFG-and BMP signaling in root development 23) in which the function and relevance of these genes have been recognized. Studies on Msx1 and Msx2 at this time are involved in bone formation and growth of skeletal and alveolar bone but reports on the development of crown and root of teeth have been scarce so far 20,24) .…”

Section: Discussionmentioning

confidence: 99%

Gene Expression During the Formation of Furcation in Porcine Tooth Germ

Nagano

Yamaguchi

Kanazashi

et al. 2012

J. Hard Tissue Biology.

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In recent years, many things have progressed and became clear in the study of genes involved in tooth development. However, the genes associated in the formation of periodontal tissues particular those studies involved in the formation of furcation are few. We have carried out a research to examine the gene expression of cementoblasts in the furcation area in porcine tooth germ. Porcine tooth germs were used as samples excised during the formation of mandibular molars and the cementoblasts around the root and at the furcation were prepared. Total RNA was isolated from the samples followed by PCR amplifying specific genes using PCR templates. Further, significant difference with respect to gene expression was determined by semi-quantitative PCR from the electrophoresis image. Also, after the removal of tooth germs, tissues were processed in routine tissue preparation, embedded in paraffin, sectioned into 5 um thickness, stained with H and E and examined under the light microscope.Amelogenin, enamelin, ameloblastin, MMP-20, Klk-4 expressions were observed uniformly by the cementoblasts at the furcation of the tooth but only amelogenin and ameloblastin were observed by the cementoblasts around the root of the tooth. Also, a typical strong Msx2 homeobox gene by the cementoblasts at the furcation was observed with an expression level of approximately 64 times than the cementoblasts around the root.The present study clearly showed that specific genes are involved in the formation of furcation. A strong Msx2 gene expression was observed in the tooth germ and even at the furcation suggesting that Msx2 plays an important role in the process of periodontal tissue formation and maturation of furcation.

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Smad4-Shh-Nfic signaling cascade–mediated epithelial-mesenchymal interaction is crucial in regulating tooth root development

Cited by 140 publications

References 49 publications

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

miRNA expression profiling identifies DSPP regulators in cultured dental pulp cells

<b>Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by </b><b>TGF-β </b>

Gene Expression During the Formation of Furcation in Porcine Tooth Germ

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