Cellular turnover in epithelial rests of <scp>M</scp>alassez in the periodontal ligament of the mouse molar

Oka, Kyoko; Morokuma, Masakazu; Imanaka‐Yoshida, Kyoko; Sawa, Yoshihiko; Isokawa, Keitaro; Honda, Masaki

doi:10.1111/eos.12003

Cited by 15 publications

(10 citation statements)

References 56 publications

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“…Subsequent discovery of LGR5 among integrin-α6 +ve stem cells of the hair follicle and other work established LGR5 as an EpiSC supermarker (Jaks et al 2008). Finally, Lgr5 marked the EpiSCs of the mouse incisor (Suomalainen and Thesleff 2010) and the ERM (Handrigan et al 2010;Oka et al 2012), meriting further investigation into LGR5 +ve cells of the human ERM (hERM).…”

Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament

Athanassiou-Papaefthymiou

Papagerakis

2015

J Dent Res

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We report a novel method for the isolation of adult human epithelial stem cells (hEpiSCs) from the epithelial component of the periodontal ligament-the human epithelial cell rests of Malassez (hERM). hEpiSC-rich integrin-α6(+ve) hERM cells derived by fluorometry can be clonally expanded, can grow organoids, and express the markers of pluripotency (OCT4, NANOG, SOX2), polycomb protein RING1B, and the hEpiSC supermarker LGR5. They maintain the growth profile of their originating hERM in vitro. Subcutaneous cotransplantation with mesenchymal stem cells from the dental pulp on poly-l-lactic acid scaffolds in nude mice gave rise to perfect heterotopic ossicles in vivo with ultrastructure of dentin, enamel, cementum, and bone. These remarkable fully mineralized ossicles underscore the importance of epithelial-mesenchymal crosstalk in tissue regeneration using human progenitor stem cells, which may have already committed to lineage despite maintaining hallmarks of pluripotency. In addition, we report the clonal expansion and isolation of human LGR5(+ve) cells from the hERM in xeno-free culture conditions. The genetic profile of LGR5(+ve) cells includes both markers of pluripotency and genes important for secretory epithelial and dental epithelial cell differentiation, giving us a first insight into periodontal ligament-derived hEpiSCs.

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Section: Introductionmentioning

confidence: 99%

Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament

Athanassiou-Papaefthymiou

Papagerakis

2015

J Dent Res

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“…The fate of epithelial cells derived from HERS has been discussed for decades. To date, various fates for HERS after fragmentation have been demonstrated: 1) incorporation in PDL maintenance as epithelial cell rests of Malassez (ERM) (7,8,18,24), 2) cell death through apoptosis (4,13), or 3) participation in cementum and PDL formation as mesenchymal cells via epithelial-mesenchymal transition (EMT) (1,20) or as epithelial cells (3,12,28). Since the number of dental epithelial cells is limited mice, which Cre-mediated recombination system driven by the keratin 14 (K14) promoter (10), with R26tdTomato mice (The Jackson Laboratory, Stock: 007909).…”

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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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“…The increases in tooth movement resulting from a weaker PDL might explain the increase in ERMs observed in transgenic mice when compared to WT. ERMs are also known to proliferate with age in homeostatic murine PDL [ 24 ]. Cell adhesion and proliferation potentially contribute to epithelial cell rest proliferation and growth within the PDL matrix.…”

Section: Discussionmentioning

confidence: 99%

SPARC and the N-propeptide of collagen I influence fibroblast proliferation and collagen assembly in the periodontal ligament

et al. 2017

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The periodontal ligament (PDL) is a fibrous connective tissue that anchors tooth cementum into alveolar bone. Secreted protein acidic and rich in cysteine (SPARC) is a collagen-binding matricellular protein known to influence collagen fiber assembly in the PDL. In contrast, functional properties of the N-propeptide of collagen I, encoded in exon 2 of the COL1A1 gene, are poorly understood. In this study, the PDL of collagen I exon 2-deleted (wt/ko), SPARC-null (ko/wt), and double transgenic (ko/ko) mice were evaluated in terms of cellularity, collagen area, fiber morphology, and extraction force and compared to WT (wt/wt) mice. Picro sirius red staining indicated a decrease in total PDL collagen content in each of the transgenic mice compared to WT at 1 and 3 month age points. At 12 months, only SPARC-null (ko/wt) and double-null PDL demonstrated less total collagen versus WT. Likewise, an increase in thin PDL collagen fibers was observed at 1 and 3 months in each transgenic, with increases only in SPARC-null and double-null mice at 12 months. The force required for tooth extraction was significantly reduced in SPARC-null versus exon 2-deleted and WT mice, whereas double-null mice demonstrated further decreases in force required for tooth extraction. The number of proliferating fibroblasts and number and size of epithelial rests of Malassez were increased in each transgenic versus WT with double-null PDL exhibiting highest levels of proliferation and rests of Malassez at 1 month of age. Consistent with increases in PDL collagen in exon-2 deleted mice, with age, numbers of rests decreased at 12 months in this genotype. These results demonstrate for the first time a functional role of the N-propeptide in regulating collagen fiber assembly and cell behavior and suggest that SPARC and the N-propeptide of collagen I have distinct activities in regulating collagen fiber assembly and fibroblast function.

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Cellular turnover in epithelial rests of Malassez in the periodontal ligament of the mouse molar

Cited by 15 publications

References 56 publications

Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament

Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament

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

SPARC and the N-propeptide of collagen I influence fibroblast proliferation and collagen assembly in the periodontal ligament

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