Differentiation capacity of BrdU label-retaining dental pulp cells during pulpal healing following allogenic transplantation in mice

Saito, Kotaro; Ishikawa, Yuko; Nakakura-Ohshima, Kuniko; Ida‐Yonemochi, Hiroko; Nakatomi, Mitsushiro; Kenmotsu, Shin-ichi; Ohshima, Hayato

doi:10.2220/biomedres.32.247

Cited by 20 publications

(8 citation statements)

References 20 publications

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“…The inconsistency between the allogenic tooth transplantation using mice and tooth replantation using rats may be attributed to the differences in host-donor interactions and/or animal species. A recent study demonstrated that numerous apoptotic cells appear in the pulp tissue including LRCs during the experimental period, suggesting that extensive apoptosis leads to elimination of donor-derived adult stem cells from the pulp tissue (Saito et al 2011a). Thus, it is assumed that the survival rate of LRCs in the allogenic tooth transplantation using mice may be different from that in autogenic tooth replantation using rats due to the differences in host-donor interactions in addition to the differences in healing patterns between two animal models mentioned above.…”

Section: Discussionmentioning

confidence: 99%

Responses of BrdU label-retaining dental pulp cells to allogenic tooth transplantation into mouse maxilla

Mutoh

Nakatomi

Ida‐Yonemochi

et al. 2011

Histochem Cell Biol

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Recently, we demonstrated that a pulse of BrdU given to prenatal animals reveals the existence of slow-cycling long-term label-retaining cells (LRCs), putative adult stem or progenitor cells, which reside in the dental pulp. This study aims to clarify responses of LRCs to allogenic tooth transplantation into mouse maxilla using prenatal BrdU-labeling, in situ hybridization for osteopontin and periostin, and immunohistochemistry for BrdU, nestin, and osteopontin. The upper-right first molars were allografted in the original socket between BrdU-labeled and non-labeled mice or between GFP transgenic and wild-type mice. Tooth transplantation caused degeneration of the odontoblast layer, resulting in the disappearance of nestin-positive reactions in the dental pulp. On postoperative days 5-7, tertiary dentin formation commenced next to the preexisting dentin where nestin-positive odontoblast-like cells were arranged in the successful cases. In BrdU-labeled transplanted teeth, dense LRCs were maintained in the center of the dental pulp beneath the odontoblast-like cells including LRCs, whereas LRCs disappeared in the area surrounding the bone-like tissue. In contrast, LRCs were not recognized in the pulp chamber of non-labeled transplants through the experimental period. Tooth transplantation using GFP mice demonstrated that the donor cells constituted the dental pulp of the transplant except for endothelial cells and some migrated cells, and the periodontal tissue was replaced by host-derived cells except for epithelial cell rests of Malassez. These results suggest that the maintenance of BrdU label-retaining dental pulp cells play a role in the regeneration of odontoblast-like cells in the process of pulpal healing following tooth transplantation.

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Section: Discussionmentioning

confidence: 99%

Responses of BrdU label-retaining dental pulp cells to allogenic tooth transplantation into mouse maxilla

Mutoh

Nakatomi

Ida‐Yonemochi

et al. 2011

Histochem Cell Biol

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“…Immunohistochemistry was conducted essentially according to our previous report (Saito, Ishikawa, et al 2011), with a mouse anti-nestin monoclonal antibody diluted to 1:500 (catalog no. MAB353, Millipore), a rabbit anti-OPN polyclonal antibody diluted to 1:5,000 (catalog no.…”

Section: Methodsmentioning

confidence: 99%

Osteopontin Is Essential for Type I Collagen Secretion in Reparative Dentin

et al. 2016

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Osteopontin (OPN) is a highly phosphorylated glycoprotein that is a prominent component of the mineralized extracellular matrix of bone. The secretion of OPN by immunocompetent cells plays a role in the differentiation of odontoblast-like cells during pulpal healing following tooth transplantation. This study aimed to clarify the role of OPN during reparative dentinogenesis. A groove-shaped cavity was prepared on the mesial surface of the upper first molars of wild-type (WT) and Opn knockout (KO) mice, and the samples were collected at intervals of 1 to 14 d. The demineralized sections were processed for immunohistochemistry for Ki67, nestin, OPN, dentin sialoprotein (DSP), integrin αvβ3, and type I collagen; in situ hybridization for Opn, col1a1, and dentin sialophosphoprotein (Dspp); and apoptosis assay. For the loss and gain of function experiments, an in vitro culture assay for evaluating dentin-pulp complex regeneration was performed. On day 1 in WT mice, odontoblasts beneath the affected dentin lost nestin immunoreactivity. On day 3, the expression of Opn was recognized at the mesial dental pulp, and OPN was deposited along the predentin-dentin border. Nestin-positive newly differentiated odontoblast-like cells expressed both Dspp and col1a1 and showed positive immunoreactivity for integrin αvβ3, DSP, and type I collagen. Until day 14, reparative dentin formation continued next to the preexisting dentin at the mesial coronal pulp. In contrast, there was no reparative dentin in the Opn KO mice where nestin- and DSP-positive newly differentiated odontoblast-like cells lacked immunoreaction for type I collagen. The in vitro organ culture demonstrated that the administration of recombinant OPN rescued the type I collagen secretion by odontoblast-like cells in the Opn KO mice. The results suggested that the deposition of OPN at the calcification front is essential for the type I collagen secretion by newly differentiated odontoblast-like cells to form reparative dentin during pulpal healing following cavity preparation.

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“…The differentiation capacity of LRCs in mice has been recently clarified after the exogenous stimuli such as allogenic tooth transplantation in our previous study: the LRCs in the transplant maintain Proliferating cells are shown in red, strong nestin-IR is shown in blue, weak nestin-IR is shown in light blue and dense LRCs are shown in green. Enamel knots in tooth germs are shown in yellow their proliferative and differentiation capacity for odontoblastlike cells (Mutoh et al 2011;Saito et al 2011). …”

Section: Mapping Of Lrcs In the Growing Toothmentioning

confidence: 99%

The relationship between cell proliferation and differentiation and mapping of putative dental pulp stem/progenitor cells during mouse molar development by chasing BrdU-labeling

et al. 2012

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Human dental pulp contains adult stem cells. Our recent study demonstrated the localization of putative dental pulp stem/progenitor cells in the rat developing molar by chasing 5-bromo-2'-deoxyuridine (BrdU)-labeling. However, there are no available data on the localization of putative dental pulp stem/progenitor cells in the mouse molar. This study focuses on the mapping of putative dental pulp stem/progenitor cells in addition to the relationship between cell proliferation and differentiation in the developing molar using BrdU-labeling. Numerous proliferating cells appeared in the tooth germ and the most active cell proliferation in the mesenchymal cells occurred in the prenatal stages, especially on embryonic Day 15 (E15). Cell proliferation in the pulp tissue dramatically decreased in number by postnatal Day 3 (P3) when nestin-positive odontoblasts were arranged in the cusped areas and disappeared after postnatal Week 1 (P1W). Root dental papilla included numerous proliferating cells during P5 to P2W. Three to four intraperitoneal injections of BrdU were given to pregnant ICR mice and revealed slow-cycling long-term label-retaining cells (LRCs) in the mature tissues of postnatal animals. Numerous dense LRCs postnatally decreased in number and reached a plateau after P1W when they mainly resided in the center of the dental pulp, associating with blood vessels. Furthermore, numerous dense LRCs co-expressed mesenchymal stem cell markers such as STRO-1 and CD146. Thus, dense LRCs in mature pulp tissues were believed to be dental pulp stem/progenitor cells harboring in the perivascular niche surrounding the endothelium.

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Differentiation capacity of BrdU label-retaining dental pulp cells during pulpal healing following allogenic transplantation in mice

Cited by 20 publications

References 20 publications

Responses of BrdU label-retaining dental pulp cells to allogenic tooth transplantation into mouse maxilla

Responses of BrdU label-retaining dental pulp cells to allogenic tooth transplantation into mouse maxilla

Osteopontin Is Essential for Type I Collagen Secretion in Reparative Dentin

The relationship between cell proliferation and differentiation and mapping of putative dental pulp stem/progenitor cells during mouse molar development by chasing BrdU-labeling

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