&lt;b&gt;Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by &lt;/b&gt;&lt;b&gt;TGF-β &lt;/b&gt;

Itaya, Satoshi; Oka, Kyoko; Ogata, Kayoko; Tamura, Shougo; Kira-Tatsuoka, Michiko; Fujiwara, Naoki; Otsu, Keishi; Tsuruga, Eichi; Ozaki, Masao; Harada, Hidemitsu

doi:10.2220/biomedres.38.61

Cited by 27 publications

(24 citation statements)

References 28 publications

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“…The dental follicle determines the growth of the periodontal ligament and the cementum and contains HERS remnants which promote dental root formation (Itaya et al, 2017). Immunofluorescent staining of the dental follicle revealed a high number of stromal cells ( Figure 1A) which were positive for FAPα but negative for E-cadherin, an epithelial cell adhesion marker.…”

Section: Identification Of Fibroblast Activation Protein-α Expressingmentioning

confidence: 99%

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Driesen

Hilkens

Smisdom

et al. 2020

Front. Cell Dev. Biol.

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Fibroblast activation protein-α (FAPα) is a membrane protein with dipeptidyl-peptidase and type I collagenase activity and is expressed during fetal growth. At the age of adolescence, FAPα expression is greatly reduced, only emerging in pathologies associated with extracellular matrix remodeling. We determined whether FAPα is expressed in human dental tissue involved in root maturation i.e., dental follicle and apical papilla and in dental pulp tissue. The dental follicle revealed a high concentration of FAPα and vimentin-positive cells within the stromal tissue. A similar observation was made in cell culture and FACS analysis confirmed these as dental follicle stem cells. Within the remnants of the Hertwigs' epithelial root sheath, we observed FAPα staining in the E-cadherin positive and vimentin-negative epithelial islands. FAPα-and vimentin-positive cells were encountered at the periphery of the islands suggesting an epithelial mesenchymal transition process. Analysis of the apical papilla revealed two novel histological regions; the periphery with dense and parallel aligned collagen type I defined as cortex fibrosa and the inner stromal tissue composed of less compacted collagen defined as medulla. FAPα expression was highly present within the medulla suggesting a role in extracellular matrix remodeling. Dental pulp tissue uncovered a heterogeneous FAPα staining but strong staining was noted within odontoblasts. In vitro studies confirmed the presence of FAPα expression in stem cells of the apical papilla and dental pulp. This study identified the expression of FAPα expression in dental stem cells which could open new perspectives in understanding dental root maturation and odontoblast function.

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Section: Identification Of Fibroblast Activation Protein-α Expressingmentioning

confidence: 99%

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Driesen

Hilkens

Smisdom

et al. 2020

Front. Cell Dev. Biol.

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“…Consistently, FS-related genes (Fras1, Frem1, Frem2) are strongly expressed at E14.5 in the developing teeth in mice (Laugel-Haushalter et al, 2013). Moreover, evidence suggests that epithelial-mesenchymal interactions are involved in dental root development (Chen et al, 2014;Itaya et al, 2017).…”

Section: Discussionmentioning

confidence: 77%

Characteristic dental pattern with hypodontia and short roots in Fraser syndrome

Kunz

Kayserili

Midro

et al. 2020

American J of Med Genetics Pt A

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Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial-mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1-FREM complex mediates critical mesenchymal-epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals.

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“…This phenomenon of cadherin switch is known as the EMT 33,34) . Recent studies represented that TGF-β stimulation could induce EMT in HERS cells 35,36) . Therefore, we postulate that CPA treatment can also facilitate EMT-like movement in the HERS cells.…”

Section: Discussionmentioning

confidence: 99%

Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

Matsuo

Toda-Nakamura

Oka

et al. 2020

J. Hard Tissue Biology.

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Cyclophosphamide (CPA) is a commonly used chemotherapeutic agent to treat cancer. Among its many side effects is the well-known consequence on tooth development when administered at early ages. This study elucidated the effects of CPA on development of the mandibular molar in mice. Mice received a single intraperitoneal injection of CPA at different doses and development times. CPA treatment led to weight loss and alopecia but had no effect on disturbances in tooth eruption or crown shape. However, at higher doses, there was arrested root development and early apical foramen closure histologically related to the formation of the cervical loop structure in the apical portion of the root. In cell culture experiments, the Hertwig's epithelial root sheath cell line (HERS01a) was cultured with or without CPA. At high doses of CPA, HERS01a cells showed decreases in E-cadherin expression, while N-cadherin expression was upregulated, indicating that this cadherin switch may promote an epithelial-to-mesenchymal transition (EMT)-like phenomenon. These findings suggest that administration of high doses of CPA can lead to arrested root development of the molars and an EMT-like phenomenon.

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

Cited by 27 publications

References 28 publications

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Dental Tissue and Stem Cells Revisited: New Insights From the Expression of Fibroblast Activation Protein-Alpha

Characteristic dental pattern with hypodontia and short roots in Fraser syndrome

Cyclophosphamide Promotes Arrested Development of the Dental Root in Mice

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