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At least 793 records · Page 44Linked to original sources
PubMed2004

Parallels between tooth development and repair: conserved molecular mechanisms following carious and dental injury.

The reparative mechanisms that operate following carious and traumatic dental injury are critical for pulp survival and involve a series of highly conserved processes. It appears that these processes share genetic programs-linked to cytoskeletal organization, cell movement, and differentiation-that occur throughout embryogenesis. Reactionary dentin is secreted by surviving odontoblasts in response to moderate stimuli, leading to an increase in metabolic activity. In severe injury, necrotic odontoblasts are replaced by other pulp cells, which are able to differentiate into odontoblast-like cells and produce a reparative dentin. This complex process requires the collaborative efforts of cells of different lineage. The behavior of each of the contributing cell types during the phases of proliferation, migration, and matrix synthesis as well as details of how growth factors control wound cell activities are beginning to emerge. In this review, we discuss what is known about the molecular mechanisms involved in dental repair.

Conserved Sequence↗
PubMed2005

NO-cGMP signaling molecules in cells of the rat molar dentin-pulp complex.

By the formation of cyclic guanosine 3',5'-monophosphate (cGMP), nitric oxide (NO)-sensitive enzyme-soluble guanylate cyclase (sGC) plays a receptor role for NO within the NO-cGMP signaling cascade, which is involved in vasodilatation and neurotransmission. The hypothesis that NO-cGMP signaling molecules modulate cells of the dentin-pulp complex was investigated in rat molars by histochemical, immunohistochemical, immuno-ultrastructural, and organ bath techniques. NO synthase (NOS) I-III, the sGC alpha(2)-subunit/beta(1)-subunit, and cGMP were detected in odontoblasts and blood vessels. NOS I, sGC alpha(2), and cGMP were identified in nerve fibers. Treatment of rat molars with the NO donor NONOate (10(-5) M) increased cGMP staining intensities in blood vessels and odontoblasts, while NO synthase inhibitor L-NAME (10(-4) M) attenuated intensity of the reaction products for cGMP, suggesting an effect of endogenous NO on sGC. These correlations of patterns and alterations of cGMP staining intensities after treatment with the NO donor or NO inhibitor might represent an NO-sGC-cGMP signaling-dependent modulation of odontoblasts, blood vessels, and nerve fibers in the dentin-pulp complex.

Animals↗
PubMed2006

Amelogenins in human developing and mature dental pulp.

Amelogenins are a group of heterogenous proteins first identified in developing tooth enamel and reported to be present in odontoblasts. The objective of this study was to elucidate the expression and function of amelogenins in the human dentin-pulp complex. Developing human tooth buds were immunostained for amelogenin, and mRNA was detected by in situ hybridization. The effects of recombinant amelogenins on pulp and papilla cell proliferation were measured by Brd U immunoassay, and differentiation was monitored by alkaline phosphatase expression. Amelogenin protein was found in the forming dentin matrix, and amelogenin mRNA was localized in the dentin, presumably in the odontoblast processes. Proliferation of papilla cells was enhanced by recombinant human amelogenin rH72 (LRAP+ exon 4), while pulp cells responded to both rH72 and rH58 (LRAP), with no effect by rH174. These studies suggest that odontoblasts actively synthesize and secrete amelogenin protein during human tooth development, and that low-molecular-weight amelogenins can enhance pulp cell proliferation.

Alternative Splicing↗
PubMed1993

Expression of plasma membrane Ca++ pump epitopes parallels the progression of enamel and dentin mineralization in rat incisor.

We investigated the expression of Ca++ pump epitopes during enamel and dentin mineralization in the rat incisor. Secretory and maturation ameloblasts were studied as well as odontoblasts, using a monoclonal antibody (5F10) against human erythrocyte plasma membrane Ca++, Mg(++)-ATPase. A progressive increase in staining intensity in ameloblasts and the odontoblasts was observed beginning with the onset of mineralization. The mainly membrane-related labeling of ameloblasts showed variable intensity depending on the stage of enamel formation, whereas that of the odontoblasts showed even intensity during continued dentinogenesis. Staining of papillary cells was evident only during enamel maturation. Western blot analysis of freeze-dried ameloblasts was also used to determine the molecular weight of the Ca++ pump epitopes as well as the distribution and relative concentration of epitopes at each stage. An immunoreactive band of MW 140 KD and lower molecular weight bands that are more intense in late than in early maturation were demonstrated. Our studies suggest that the expression of plasma membrane Ca++ pump parallels the progression of mineralization in rat incisor enamel and dentin.

Ameloblasts↗
PubMed1991

Associations between transforming growth factor beta 1 RNA expression and epithelial-mesenchymal interactions during tooth morphogenesis.

We have studied the expression of transforming growth factor beta-1 (TGF-beta 1) RNA during mouse tooth development, using in situ hybridization and experimental tissue recombinations. Analysis of the serial sections revealed the appearance of local expression of TGF-beta 1 RNA in the dental epithelium at bud-staged teeth (13-day embryos). Just before transition to the cap stage, TGF-beta 1 RNA expression rapidly increased in the epithelial bud, and it also extended to the condensed dental mesenchyme. At cap stage (14- and 15-day embryos), there was an intense expression of TGF-beta 1 RNA in the morphologically active cervical loops of the dental epithelium. During early bell stage (16- and 17-day embryos), TGF-beta 1 RNA expression was detected in the inner enamel epithelium where it subsequently almost disappeared (18-day embryos). After birth TGF-beta 1 transcripts transiently appeared in these cells when they were differentiating into ameloblasts (1-day mice). The transcripts were lost from the ameloblasts when they became secretory (4-day mice), but the expression continued in ameloblasts in enamel-free areas. Transient expression of TGF-beta 1 RNA was also detected in epithelial stratum intermedium cells at the time of ameloblast differentiation. In the mesenchyme, TGF-beta 1 RNA was not detected during bell stage until it appeared in differentiated odontoblasts (18-day embryos). The secretory odontoblasts continued to express TGF-beta 1 RNA at all stages studied including the odontoblasts of incisor roots. Analysis of the distribution of bromodeoxyuridine (BrdU) incorporation indicated apparent correlations between TGF-beta 1 RNA expression and cell proliferation at the bud and cap stages but not at later stages of tooth development. Tissue recombination experiments of bud-staged (13-day embryos) dental and non-dental tissues showed that tooth epithelium, when cultured together with tooth mesenchyme, expressed TGF-beta 1 RNA. When the tooth epithelium was combined with non-dental jaw mesenchyme, TGF-beta 1 transcripts were not expressed. However, TGF-beta 1 RNA expression was seen in oral epithelium cultured with dental mesenchyme, while no expression of TGF-beta 1 transcripts was seen in the oral epithelium during normal development. Thus, TGF-beta 1 RNA expression seems to be regulated by epithelial-mesenchymal interactions.

Animals↗
PubMed2003

Distribution of biglycan and decorin in rat dental tissue.

Biglycan and decorin are small leucine-rich proteoglycans that play several biological and structural roles in different tissues and organs. Several reports have indicated that biglycan participates in odontoblast and ameloblast differentiation and in the calcification process. In the present study we show that the expression of biglycan changes from within the ameloblasts and odontoblasts to the extracellular space according to the stage of animal development. In predentin and in the pulp space, however, biglycan was continually expressed throughout the period of investigation. In contrast, decorin was absent in odontoblasts and in ameloblasts and was exclusively expressed in predentin throughout the period of observation. In young rats, however, decorin was expressed in the extracellular spaces of the pulp, where it was concentrated mainly in the peripheral pulp.

Ameloblasts↗
PubMed2006

Human dental pulp cell culture and cell transplantation with an alginate scaffold.

Many studies on tissue stem cells have been conducted in the field of regenerative medicine, and some studies have indicated that cultured dental pulp mesenchymal cells secrete dentin matrix. In the present study we used alginate as a scaffold to transplant subcultured human dental pulp cells subcutaneously into the backs of nude mice. We found that when beta-glycerophosphate was added to the culture medium, dentin sialophosphoprotein mRNA coding dentin sialoprotein (DSP) was expressed. An increase in alkaline phosphatase, which is an early marker for odontoblast differentiation, was also demonstrated. At 6 weeks after implantation the subcutaneous formation of radio-opaque calcified bodies was observed in situ. Immunohistochemical and fine structure studies identified expression of type I collagen, type III collagen, and DSP in the mineralizing transplants. Isolated odontoblast-like cells initiated dentin-like hard tissue formation and scattered autolyzing apoptotic cells were also observed in the transplants. The study showed that subcultured dental pulp cells actively differentiate into odontoblast-like cells and induce calcification in an alginate scaffold.

Alginates↗
PubMed2006

Isolated rat dental pulp cell culture and transplantation with an alginate scaffold.

Many studies have been conducted on tissue stem cells in the field of regenerative medicine, and cultured dental pulp mesenchymal cells have been reported to secrete dentin matrix. In the present study we used alginate as a scaffold to transplant subcultured rat dental-pulp-derived cells subcutaneously into the back of nude mice. We found that when beta-glycerophosphate was added to the culture medium, the mRNA of the dentin sialophosphoprotein (DSPP) gene coding dentin sialoprotein (DSP) and dentin phosphoprotein (DPP) was expressed, and an increase in alkaline phosphatase, an early marker of odontoblast differentiation, was also demonstrated. Six weeks after implantation, subcutaneous formation of radiopaque calcified bodies was observed in situ. Immunohistochemical and fine structure studies identified expression of type I collagen, type III collagen, and DSP in the mineralizing transplants, and isolated odontoblast-like cells began to form dentin-like hard tissue formation. Scattered autolyzing apoptotic cells were also observed in the transplants. The study showed that subcultured rat dental-pulp-derived cells actively differentiate into odontoblast-like cells and induce calcification in an alginate scaffold.

Alginates↗
PubMed1985

Renewal and migration of rat incisor mesenchymal cells after doxorubicin administration.

Ten female rats were intravenously injected with doxorubicin (20 mg/kg) and divided into two equal groups receiving a dose of tritiated thymidine either simultaneously with doxorubicin or 1 h before being killed after 5 days. Six control animals were correspondingly injected with 3H-thymidine. The left and right maxillary incisors were prepared for histologic and microautoradiographic investigation, respectively. The distribution of labeled cells in animals injected 1 h before death showed the regions of proliferation, whereas migration from these regions was evaluated by longer observation time. A zone of reduced dentin deposition lined by irregular odontoblasts being young odontoblasts and late preodontoblasts was observed at the time of doxorubicin injection. Pulpally to the dentinal lesion, islands of irregular predentin were deposited by non-progenitive pulp cells and depolarized odontoblasts. The late preodontoblasts were renewed from progenitive pulp cells, leading to a disturbed mantle predentin deposition.

Animals↗
PubMedDate not supplied

[Effects of cytochalasin B and colchicine on dental cytodifferentiation in vitro].

The effects of various concentrations of cytochalasin B and colchicine on the polarization of odontoblasts and ameloblasts of mouse tooth buds cultivated in vitro, were studies. It was shown that cytochalasin B, deside its action on the microfilaments, had important cytotoxic effects; dilatation of the odontoblast's processus, accumulation of secretory granules in the Golgi apparatus, dilatation of mitochondria, inhibition of polarization or depolarization of odontoblasts and ameloblasts. These modifications resulted chiefly from the lesion of microtubules which seem to play an important role in the polarization of the cells studies.

Ameloblasts↗
PubMed1992

Dentin extracellular matrix and dentinogenesis.

The formation of dentin involves secretion of matrix proteins by odontoblasts, prior to the deposition of apatite crystals. These matrix proteins probably play a role in transformation of predentin to dentin. The physical and chemical properties of dentin collagen, similar to those of bone, are especially adapted for binding matrix proteins and as a grid for mineral deposition. Phosphophoryns, polyanionic, and dentin-specific proteins are secreted at the mineralization front and are involved in some way in the mineralization process of circumpulpal dentin. Dentin sialoprotein is specifically made by odontoblasts and pulp cells and may be in the family of bone proteins known to promote cell attachment. Several proteins originally isolated from bone are also found in dentin and are expressed by odontoblasts. Although the mechanisms of dentinogenesis have not been elucidated, detailed studies of dentin matrix proteins should give valuable insights into this process.

Collagen↗
PubMed2005

[Expression of Runx2/Cbfa1 in the developing pulpo-dentinal complex of postnatal mice].

OBJECTIVE: To study the expression of Runx2/Cbfa1 in the developing dentin and differentiating odontoblasts. METHODS: A postnatal mice teeth developing model was built histologically. Immunohistochemical technique was adopted to determine the expression of Runx2/Cbfa1 in the developing pulpo-dentinal complex in mice. RESULTS: Runx2/Cbfa1 was merely present in predentin in the exact and before the 11th day's postnatal stages. Meanwhile, it was positively located in odontoblasts and dental pulp cells in root region, but negatively in coral part after the 11th day's stages. CONCLUSION: Runx2/Cbfa1 may play an important role in the deposing of tooth dentin and in the differentiating of odontoblasts and pulp cells.

Animals↗
PubMed1988

The ultrastructure of dentine from rat incisors following exposure to sodium fluoride and potassium pyroantimonate staining.

Weanling rats were given a single intraperitoneal injection of sodium fluoride and control animals normal saline for four consecutive days. The fluoride produced a consistent response in the mineralizing dentine of the incisors in which a hypermineralized band was succeeded by a hypomineralized band. Potassium pyroantimonate staining for calcium ions showed that following injection of fluoride, in contrast to the controls, there were large amounts of calcium pyroantimonate in the pre-dentine and throughout the odontoblasts. This suggests that fluoride temporarily affects the membrane enzyme systems which maintain calcium concentration gradients between the odontoblasts and the matrix. The resultant influx of calcium is probably associated with the hypermineralization of the dentine matrix in which more hydroxyapatite crystallites are deposited. Upon recovery of the odontoblasts the matrix is relatively depleted of calcium resulting in matrix hypomineralization.

Animals↗
PubMed1978

Action of 5-bromodeoxyuridine on tooth germs "in vitro." I. - Effects on cytodifferentiation.

Sixteen or eighteen day old mouse embryonic first lower molars were treated with 5-bromodeoxyuridine (BrdU) in vitro. --In 16-day old tooth germs cytodifferentiation of both odontoblasts and ameloblasts was inhibited. This inhibition was reversible. --In 18-day old tooth germs, the odontoblasts localized at the top of the principal cusps (post-mitotic cells) differentiated normally and secreted predentin. In these conditions ameloblasts localized in front of functional odontoblasts differentiated, although they were able to incorporate BrdU. --In others experiments, control and BrdU-treated tooth germs were dissociated into enamel organs and pulps. Cultivated associations between either control or BrdU treated pulps with either control or BrdU treated enamel organs were analyzed. It appeared that the primary effect of BrdU might result in its incorporation in the preameloblasts which were no longer able to interact normally with the preodontoblasts.

Ameloblasts↗
PubMed1987

Developmental appearance of Gla proteins (osteocalcin) and alkaline phosphatase in tooth germs and bones of the rat.

The tissue distribution and developmental appearance of alkaline phosphatase and Gla proteins, relative to mineralization were examined. Undecalcified sections of tooth germs, calvaria and alveolar bone of the rat were immunostained for Gla proteins, (indirect immunofluorescence and avidin-biotin-peroxidase-complex) and then stained for alkaline phosphatase activity. In the growth regions of tooth germs, Gla protein was observed in young odontoblasts and in early predentin, at a stage prior to formation of the first mineralized dentin. Similar results were obtained for bone: young osteoblasts as well as osteoid were immunopositive for Gla protein prior to formation of the first mineralized bone. Histochemical staining revealed that differentiating odontoblasts and osteoblasts exhibited alkaline phosphatase activity at stages prior to appearance of Gla proteins and that cells adjacent to odontoblasts and osteoblasts (not directly involved in the formation of predentin/dentin and osteoid/bone) stained for alkaline phosphatase, but not for Gla proteins. We conclude, that in these bone- and dentin-forming cells, alkaline phosphatase activity is expressed before the appearance of Gla proteins, but that both appear before the onset of mineralization. We also conclude that Gla protein is a more specific marker for bone and dentin formation than histochemical alkaline phosphatase activity, since only the cells directly involved in these processes were immunostained for Gla protein.

Alkaline Phosphatase↗
PubMed1984

Dentino-pulpal collagen and the incorporation of 3H-proline by sound and carious human teeth in vitro.

In vitro incorporation of proline by odontoblasts and pulpal cells of human carious and non-carious teeth was compared. The types of collagen in predentine and pulpal matrices of carious as well as intact teeth were characterized electrophoretically. The results indicate increased incorporation in the caries-affected odontoblast-predentine layer, with no quantitative changes in the adjacent pulp tissue. The predentine matrix of both intact and carious teeth showed an electrophoretic banding typical to type I collagen. The pulpal matrix, regardless of the state of the tooth, displayed a mixture of collagen types I and III, the former being clearly predominant. It seems that a carious process in dentine increases the collagen forming activity in the adjacent odontoblasts, but does not affect the quality or alter the relative proportion of the collagen types I and III.

Adult↗
PubMed1983

[35S]autoradiographic study of sulfated GAG accumulation and turnover in embryonic mouse tooth germs.

The accumulation of sulfated GAG in embryonic mouse molars before, during, and after terminal differentiation of odontoblasts was localized by [35S]autoradiography combined with the use of chondroitin ABC lyase. Much more sulfated GAG were accumulated in the dental papilla than in the dental epithelium. High incorporation of [35S]sulfate occurred at the epithelio-mesenchymal junction, which is the site of dental basement membrane and predentin. Before terminal differentiation of odontoblasts, the distribution of sulfated GAG was uniform at the basement membrane. After the onset of terminal differentiation of odontoblasts, much more sulfated GAG accumulated at the tip of principal cusps than at the apical (inferior) parts of cusps, and sulfated GAG were then found to be degraded more rapidly at the epithelio-mesenchymal junction than at other parts of the tooth germ. Thus regional variation in the rate of degradation of GAG exists in the tooth germs. Trypsin-isolated dental epithelia cultured in vitro synthesized a new basement membrane that could be labeled with [3H]glucosamine but not with 35SO4(-2). The epithelial-derived basal lamina contains little or no sulfatated GAG.

Animals↗
PubMed1981

Ultrastructure of the epithelial-mesenchymal interface in the mouse tooth germ.

The structure of the epithelial-mesenchymal interface of a developing mouse embryonic tooth germ was examined at the time of cell differentiation by using transmission and scanning electron microscopy. During odontoblast differentiation, the basal lamina was continuous beneath the inner enamel epithelium, and the fibrils at the mesenchymal aspect increased in density and length. Numerous cell processes of the preodontoblasts were seen in close contact with the basal lamina. This supports the idea that the basement membrane is involved in the differentiation of mesenchymal cells into odontoblasts, probably by providing special attachment sites for the aligning mesenchymal cells. The rearrangement of intracellular organelles in the cells of enamel epithelium and a change of epithelial morphology were already seen at the time of the initial predentin secretion by odontoblasts. At this time, the basal lamina was still present. The penetration of epithelial microvilli into the epithelial-mesenchymal interface through breaks in the basal lamina related to the onset of predentin mineralization. This suggests that the determination of epithelial cells into ameloblasts already occurs before the disappearance of the basal lamina.

Ameloblasts↗