Mapping of BrdU label-retaining dental pulp cells in growing teeth and their regenerative capacity after injuries

Ishikawa, Yuko; Ida‐Yonemochi, Hiroko; Suzuki, Hiromu; Nakakura-Ohshima, Kuniko; Jung, Han Sung; Honda, Masaki; Ishii, Yumiko; Watanabe, Nobuyuki; Ohshima, Hayato

doi:10.1007/s00418-010-0727-5

Cited by 54 publications

(59 citation statements)

References 42 publications

(51 reference statements)

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“…The present immunohistochemistry for nestin confirmed that nestin is valuable as a differentiation marker for odontoblasts (26). Furthermore, our double immunohistochemistry for nestin and Dsp proteins clearly demonstrated that the timing of their expressions in the odontoblast-lineage cells was synchronized: preodontoblasts began to express both proteins and increased their intensity according to the progress of odontoblast differentiation, and finally mature odontoblasts showed intense expression of both proteins in their cytoplasm.…”

Section: Nestinsupporting

confidence: 80%

“…The present study clearly demonstrated that the expression of Dsp mRNA coincided with the odontoblast secretory activity for dentin matrix deposition in both 3-week-old incisors and developing molars, judging from the previous data: the rate of dentin deposition in the medial coronal portion almost ceases after 60 days in rats (57) and the progress of dentinogenesis in mice is faster than that in rats (26,27). In contrast, other pulpal cells, predentin matrix and dentinal tubules showed positive reactions only for Dsp protein and increased in their intensity according to the progress of tooth development.…”

Section: Dspsupporting

confidence: 78%

“…A digoxigenin-labeled probe for Dsp mRNA (43) was prepared according to the manufacturer's protocol. Following the fixation, the specimens were decalcified with Morse's solution (10% sodium citrate and 22.5% formic acid) for 24 h (47), dehydrated through ethanol series and xylene, and embedded in pearing following tooth injuries such as cavity preparation and tooth replantation/transplantation (1,24,26,28,36,46,54). Regarding immunohistochemistry for Dmp1, we failed to obtain a specific immunoreaction in the differentiated odontoblasts in our preliminary experiments (data not shown).…”

mentioning

confidence: 99%

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Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

et al. 2012

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Differentiated odontoblasts could not be identified by one unique phenotypic marker, but the combination of expression of dentin phosphoprotein (Dpp), dentin sialoprotein (Dsp), dentin matrix protein 1 (Dmp1), and nestin may be valuable for the assessment of these cells. However, the findings using these proteins remain controversial. This study aimed to compare two odontoblast differentiation markers: nestin and Dsp in the process of dentinogenesis in mice. We performed immunohistochemistry and/or in situ hybridization technique for nestin and Dsp using 3-week-old incisors as well as postnatal 1-day-to 8-week-old molars. Preodontoblasts began to express nestin and Dsp proteins and Dsp mRNA, which increased in their intensity according to the progress of odontoblast differentiation in both incisors and developing molars. Nestin was consistently expressed in the differentiated odontoblasts even after the completion of dentin matrix deposition. The expression of Dsp mRNA coincided with the odontoblast secretory activity for dentin matrix deposition. In contrast, other pulpal cells, predentin matrix and dentinal tubules also showed a positive reaction for Dsp protein in addition to differentiated odontoblasts. In conclusion, nestin is valuable as a differentiation marker for odontoblasts, whereas Dsp mRNA is a functional marker for their secretory activity.Dentin is a hard connective tissue that forms the bulk of the tooth, and it is a bone-like matrix characterized by multiple closely packed dentinal tubules that traverse its entire thickness and contain the cytoplasmic processes of odontoblasts, which are responsible for the formation and maintenance of the dentin. The cell bodies of the odontoblasts are aligned along the inner aspect of the dentin, beneath a layer of predentin, where they also form the peripheral boundary of the dental pulp (35). The odontoblasts are terminally differentiated ectomesenchymal cells that synthesize several collagenous and non-collagenous proteins (NCPs) (45). The morphologically discernible differentiation of the odontoblast begins with the dental papilla cells adjacent to the inner enamel epithelium (7). The dental papilla cells adjoining the acellular zone rapidly enlarge and elongate to become preodontoblasts first and then odontoblasts as their cytoplasm increases in volume to contain increasing amounts of proteinsynthesizing organelles. The morphology of odontoblasts reflects their functional activity and ranges from an active synthetic phase to a quiescent phase (35). However, the preferred use of terminology regarding the classification of odontoblasts is controversial, because several terms for differentiated odontoblasts have been used by different researchers, i.e., secretory, transitional, and aged odontoblasts (12), young and old odontoblasts (51), or

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Section: Nestinsupporting

confidence: 80%

Section: Dspsupporting

confidence: 78%

mentioning

confidence: 99%

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Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

et al. 2012

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“…Inactivation of IGF-1R and p38 MAPK by their respective inhibitors, sc204008 and PD169316, induced Ki67 in DPCs ex vivo and decreased the quiescence of PY low and G0-arrested human DPSCs cells in vitro, demonstrating that p38 MAPK and IGF-1R are responsible for the mitotic quiescence of these cells. The identity of DPSCs was corroborated by their phenotype, stem cell activity, and localization of Ki67-positive cells perfectly matching the position of BrdU-positive DPSCs reported by Téclès et al [4] and Ishikawa et al [19] and the position of Oct4-positive pluripotent DPSCs reported in another study [74]. Taken together, our data establish that IGF-1R and p38 MAPK signaling pathways control human DPSC quiescence and demonstrate that these pathways must be inactivated for mitotic division to occur in DPSCs.…”

Section: Discussionsupporting

confidence: 84%

“…A study based on the mRNA expression levels of DPSC markers, including CD166, CD146, and CD105, concluded that in rat molars, ''coronal pulp harbors more SCs than the other regions'' [17]. A study by Ishikawa et al [18,19] determined that 5-bromo-2¢-deoxyuridine (BrdU)-retaining cells expressing the mesenchymal stem cell marker CD146 were associated with vessels located in the central region of adult rat dental pulp. These label retaining cells (LRCs) possessed proliferative capacity and were responsible for the regeneration of damaged odontoblasts.…”

Section: Introductionmentioning

confidence: 99%

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

Vandomme

Touil

Ostyn

et al. 2014

Stem Cells and Development

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Dental pulp stem cells (DPSCs) remain quiescent until activated in response to severe dental pulp damage. Once activated, they exit quiescence and enter regenerative odontogenesis, producing reparative dentin. The factors and signaling molecules that control the quiescence/activation and commitment to differentiation of human DPSCs are not known. In this study, we determined that the inhibition of insulin-like growth factor 1 receptor (IGF-1R) and p38 mitogen-activated protein kinase (p38 MAPK) signaling commonly activates DPSCs and promotes their exit from the G0 phase of the cell cycle as well as from the pyronin Y low stem cell compartment. The inhibition of these two pathways, however, inversely determines DPSC fate. In contrast to p38 MAPK inhibitors, IGF-1R inhibitors enhance dental pulp cell sphere-forming capacity and reduce the cells' colony-forming capacity without inducing cell death. The inverse cellular changes initiated by IGF-1R and p38 MAPK inhibitors were accompanied by inverse changes in the levels of active signal transducer and activator of transcription 3 (STAT3) factor, inactive glycogen synthase kinase 3, and matrix extracellular phosphoglycoprotein, a marker of early odontoblast differentiation. Our data suggest that there is cross talk between the IGF-1R and p38 MAPK signaling pathways in DPSCs and that the signals provided by these pathways converge at STAT3 and inversely regulate its activity to maintain quiescence or to promote self-renewal and differentiation of the cells. We propose a working model that explains the possible interactions between IGF-1R and p38 MAPK at the molecular level and describes the cellular consequences of these interactions. This model may inspire further fundamental study and stimulate research on the clinical applications of DPSC in cellular therapy and tissue regeneration.

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Research advances in tissue regeneration by dental pulp stem cells

Waddington

Sloan

2016

Tissue Engineering and Regeneration in Dentistry

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Mapping of BrdU label-retaining dental pulp cells in growing teeth and their regenerative capacity after injuries

Cited by 54 publications

References 42 publications

Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

Expression patterns of nestin and dentin sialoprotein during dentinogenesis in mice

Insulin-Like Growth Factor 1 Receptor and p38 Mitogen-Activated Protein Kinase Signals Inversely Regulate Signal Transducer and Activator of Transcription 3 Activity to Control Human Dental Pulp Stem Cell Quiescence, Propagation, and Differentiation

Research advances in tissue regeneration by dental pulp stem cells

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