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Heritable dentin defects: nosology, pathology, and treatment.

Heritable dentin defects have been divided into 2 main categories: dentinogenesis imperfecta (DI) and dentin dysplasia (DD). Recent studies have shown that they share many features in common. Of the connective tissue diseases, only osteogenesis imperfecta (OI) has been linked to these disorders. So far, no definitive relation between the type of OI and the dental involvement can be established. Familial occurrence of DI with OI cannot be comprehensively explained by mutations in type I collagen genes. No information about the gene defects in DD is available. At the ultrastructural level, the organization of the normally cross-striated collagen fibers in the dentin matrix varies markedly in patients affected by DI.

Dentin Dysplasia↗

Molecular basis of human dentin diseases.

In recent years, substantial progress has been made regarding the molecular etiology of human structural tooth diseases that alter dentin matrix formation. These diseases have been classified into two major groups with subtypes: dentin dysplasia (DD) types I and II and dentinogenesis imperfecta (DGI) types I-III. Genetic linkage studies have identified the critical loci for DD-II, DGI-II, and DGI-II to human chromosome 4q21. Located within the common disease loci for these diseases is cluster of dentin/bone genes that includes osteopontin (OPN), bone sialoprotein (BSP), matrix extracellular phosphoglycoprotein (MEPE), dentin matrix protein 1 (DMP1), and dentin sialophosphoprotein (DSPP). To date, only mutations within dentin sialophosphoprotein have been associated with the pathogenesis of dentin diseases including DGI types-II and -III and DD-II. In this article, we overview the recent literature related to these dentin genetic diseases, their clinical features, and molecular pathogenesis.

Chromosome Mapping↗

Odontoblast turnover in the impeded and unimpeded rat incisor derived from computerized histomorphometry.

A computerized histomorphometric method was devised to estimate the kinetics of odontoblast turnover and dentinogenesis in rat incisors. The method was applied to two groups of rats: one group with lower incisors in impeded eruption and another group with the left lower incisor in the unimpeded state. The teeth were divided into six equal segments, from which consecutive ground sections were obtained. The distance of each ground section from the posterior border of the alveolar bone was calculated. Each section was magnified, traced, and the tracings fed into a computer by a sonic digitizer. The perimeters and areas of dentine and pulp in each ground section were calculated by the computer. The mean odontoblast density along the predentine was evaluated from histological sections taken both from the same tooth segments and from teeth sectioned midsagittally. These served for the estimation of the predentine area occupied by the average odontoblast. In the impeded group, this area was 11% larger than in the unimpeded one. Outer dimensions of teeth, namely the circumference of the dentine, the labiolingual width, and the mesiolateral width remained constant and equal for both groups. Daily rates of dentine apposition were computed and were found to vary according to the age of the odontoblasts. Odontoblasts of impeded teeth started to secrete matrix at a rate of 17 microns/day, which increased slightly to 19 microns/day and later declined to 7 microns/day on the 38th day. Dentine production of unimpeded odontoblasts, on the other hand, started at a rate of 16 microns/day and gradually increased to 34 microns/day on the 17th day.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Mineralization patterns in elasmobranch fish.

This article reviews current findings on the organic matrix and the mineralization patterns in elasmobranchs, including an analysis of the role of the dental epithelial cells and the odontoblasts during odontogenesis. Our electron micrographs demonstrated that tubular vesicles limited by a unit membrane occupied the bulk of the elasmobranch enameloid matrix during the stage of enameloid matrix formation. It is likely that the tubular vesicles originated from the odontoblast processes. Two types of electron-dense fibrils, with cross-striations at intervals of approximately either 17 nm or 55 nm, respectively, were detected in the enameloid matrix. These data suggest that odontoblasts were strongly involved in enameloid matrix formation and in initial enameloid mineralization. Two types of odontoblasts, dark and light cells, were recognized during the stage of dentinogenesis. The light cells contained numerous mitochondria, intermediate filaments, and microtubules that extended their processes into the dentin. The dark cells possessed a well-developed Golgi apparatus and many cisternae in the rough endoplasmic reticulum, which suggests that the dark cells are involved in the formation of dentin. The inner dental epithelial (IDE) cells exhibited a well-developed Golgi apparatus, many mitochondria, cisternae of smooth endoplasmic reticulum, vesicles, vacuoles, and granules during the mineralization and maturation stages. During the stages of mineralization and early maturation, ACPase-positive granules were visible in the IDE cells and ALPase and Ca-ATPase activities were found at the lateral and proximal cell membrane of the IDE cells, suggesting that the IDE cells are involved in the removal of enameloid organic matrix and in the process of mineralization during later stages of enameloid formation. Our data indicate that elasmobranch enameloid is distinct from teleost enameloid, based on its organic content, on the mechanisms of its mineralization, and on the role of IDE cells concerning enameloid formation.

Animals↗

Treatment of dental decay by CO2 laser beam: preliminary results.

Results obtained from two clinical cases, representative of 1,140 human teeth treated by CO2 laser beam during 3 years, announce a new conception of treatment of dental caries. The beam (P = 4 - 5 W, energy density of 9 to 25 kw/cm2) causes a dentin healing which becomes sterile, chemically and physically more resistant than pathological dentin. In addition, this exposure leads to an activation of the dentinogenesis supported by X-ray, confirming histo-pathological results obtained from experiments performed on animals.

Adolescent↗

Tools for tissue engineering of mineralized oral structures.

This paper presents a short review of three groups of tools which can be or are used for the tissue engineering of mineralized oral structures: growth factor delivery systems (GFDS) and surface bioactivation with covalent bound peptides or with nanomechanically linked proteins. According to the reported personal experience of the authors, GFDS have to face the following challenging issue before being used routinely in dentistry, e.g., as a tool for reparative dentinogenesis or bone healing: adaptation of the GFDS design to the tissue where it will be implanted in order to deliver the right dose of growth factor (GF) at the right time. The bioactivation of surfaces, for example of dental implants, with covalent bound peptides or nanomechanically linked proteins represents a second innovative way to improve dental health in the future. Here we report on the experimental use of cyclic RGD peptides grafted on polymethylmethacrylate to improve osteoblast adhesion. Furthermore, we show the potential advantage of immobilizing and incorporating collagen I on titanium implant surfaces. These techniques or a combination of them will help to create improvements, for example, of dental implants in the near future. They will also help to promote bone and dentin regeneration.

Alveolar Process↗

Regulation of tenascin expression in cultured rat dental pulp cells.

Tenascin (TN) is a glycoprotein of extracellular matrix abundantly present in embryonic mesenchymal tissues. Transforming growth factor-beta1 (TGF-beta1), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), hepatocyte growth factor (HGF), and retinoic acid (RA) are important regulators of dentinogenesis. Dental pulp cells have the capacity to differentiate into odontoblast-like cells. In this study, we investigated the effects of growth factors on TN expression and adhesive function using rat clonal dental pulp cells, RPC-C2A. Analyses of reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting revealed that RPC-C2A cells expressed TN molecules and that TGF-beta1, HGF, and RA increased expression of TN at the mRNA and protein level, while bFGF and EGF showed a weak effect. An adhesion assay revealed that treatment with TGF-beta1, HGF, and RA induced a marked reduction of cell attachment to fibronectin (FN)-coated surfaces, whereas there was no change with bFGF and EGF. Functional blocking of growth factor-stimulated TN protein by pretreating cells with anti-TN antibodies restored cell attachment to control levels. These findings suggest that TGF-beta1, HGF, and RA may regulate pulpal cell adhesion to FN-coated surfaces and that this effect is mediated by TN.

Animals↗

Effect of prolonged iron deficiency on enamel pigmentation and tooth structure in rat incisors.

The effect of iron deficiency maintained for over 6 months on the pigmentation and structure of incisors was investigated in female white rats. Gross loss of pigmentation was observed. Sections revealed enamel hypoplasia and aplasia. Dentinogenesis was much less affected, but there were areas of altered dentine with abnormal tubules and increased thickness of predentine with cellular and vascular inclusions.

Anemia, Hypochromic↗

Organ culture study of effect of vitamin-A-deficiency on rat third molar development.

A culture procedure for rat third molars suitable for nutritional-developmental studies is described. Unerupted third molars from 12-day-old rats were cultured in BGJb media containing 20 per cent rat serum and supplemented with 25 mM HEPES buffer, 25 mg ascorbic acid, 20 mg L-glutamine, 12 mg penicillin G and 10 mg streptomycin sulphate per 100 ml of media. Molars were cultured at the liquid-gas interphase using a 50 per cent O2, 45 per cent N2, 5 per cent CO2 gas mixture at 10 lb-psig (pounds per square inch guage). Molar cultures were maintained successfully for 9-14 days without evidence of necrosis, although they developed at a slower rate than in vivo. Molars cultured in 50 per cent O2 compared to those cultured in 21 per cent O2 for periods of 2, 4, 6 and 8 days had higher values for protein, alkaline phosphatase (AP), Ca, P and Ca/P. Vitamin-A-deficiency gave lower values for AP, Ca, P, Ca/P, 45Ca, 35S and [14C]-proline uptake. Histologically, A - molars had atrophic ameloblasts, some foci of squamous metaplasia and abnormal keratin formation. Thus, deficiency of vitamin A imposed during in-vitro development of rat third molars retarded dentinogenesis and interfered with early mineralization of enamel and dentine.

Aging↗

The effect of ovariectomy and high-sucrose diet on dentine formation and caries in growing rats.

Ovariectomized (Ovx) or sham-operated (Cnt) and tetracycline-labelled growing rats were fed either a commercial powdered standard rat diet (Ovx and Cnt) or a high-sucrose diet (Ovxsuc and Cntsuc). All animals were inoculated in the mouth with Streptococcus sobrinus. At 11 weeks of age the areas of caries lesions and dentinal apposition of the first and second molars and the areas of the pulpal cross-section of the incisors were determined. The area of dentinal apposition was largest in Cnt animals, the difference being statistically significant only in comparison with the Cntsuc animals. No such difference between the diets was found among the Ovx animals. The cross-section of the pulpal chamber was smallest in the Ovxsuc rats and largest in the Cnt animals, but no statistically significant differences were found between the groups. The caries lesions were significantly larger in Ovx, Ovxsuc and Cntsuc animals than in Cnt ones. Ovariectomy thus increased caries progression in growing rats, but the effect on dentine formation remained negligible. In this respect there is a difference between primary and secondary dentinogenesis.

Analysis of Variance↗

Ultrastructural relation between nerve terminals and dentine bridge formation after pulpotomy in human teeth.

Close association between nerve terminals and preodontoblasts, odontoblasts and predentine was observed during healing after pulpotomy. The nerve terminals frequently contained large numbers of synaptic vesicles. Terminals with many vesicles tended to be fewer in the predentine than in the odontoblastic layer. The distribution of terminals was more dense at the stage before the regenerated odontoblasts became arranged regularly beneath the predentine. It is suggested that these terminals have some efferent role(s), especially during collagen synthesis at the early stage of dentinogenesis. The nerves may release their abundant synaptic vesicles, in addition to serving a sensory role for monitoring the increased sensitivity in the injured areas.

Dentin, Secondary↗

Morphological analysis of dentine formation in young rat molars during the recovery phase with calcium alone or combined with xylitol following a low-calcium dietary regimen.

The effects of dietary calcium deficiency and subsequent replenishment of the diet with calcium alone or with xylitol were studied. Thirty 3-week-old Wistar rats were labelled with an i.p. tetracycline injection. Twenty rats were fed a diet with 0.026% calcium (Ca-deficient); 10 received a 0.5% Ca diet (controls). After 3 weeks the tetracycline labelling was repeated. Replenishment of the diet was introduced for Ca-deficient rats, and 10 received additional 5% xylitol in the diet. After 4 weeks the labelling was repeated and the animals were decapitated. Dentine formation was measured by the tetracycline stripes in the lower first and second molars. Calcium deficiency during the first 3 weeks reduced dentine formation. In the control and xylitol groups, a much smaller amount of dentine was formed during the recovery period. With Ca alone, dentine formation was faster than in the controls or Ca-xylitol group and did not differ from the Ca-deficient period. These results indicate that in rat molars the odontoblasts can accelerate the rate of dentine formation when calcium is restored to the diet, at least during primary dentinogenesis. This effect was not seen when 5% xylitol was added to the replenishment diet.

Animals↗

Partial cDNA sequencing of mouse dentine sialoprotein and detection of its specific expression by odontoblasts.

Dentine sialoprotein (DSP), a 53-kDa acidic glycoprotein, is expressed by odontoblasts and secreted into the dentine extracellular matrix. Although little is known about its biological function, it might play a part in dentinogenesis. Because DSP has only been shown to occur in rat dentine, it is important to demonstrate its existence in another species. Here, the presence of DSP gene in the mouse genome, and the cloning of a mouse DSP cDNA coding for about one-fifth of the molecule with a nucleotide sequence similar to that for rat cDNA, are reported. Using in-situ hybridization, DSP mRNA was uniquely detected in mouse odontoblasts.

Animals↗

Comparison of Dycal and formocresol pulpotomies in young permanent teeth in monkeys.

This study compared Dycal and formocresol pulpotomies on young healthy permanent teeth with respect to continued dentinogenesis and root end development. Pulpotomy was performed on a total of forty permanent teeth with incompletely developed roots in three young stump-tailed monkeys (Macaca speciosa). Twenty teeth were treated with Dycal and twenty with formocresol. At the end of the experimental periods the animals were killed and the specimens were prepared and sectioned en bloc for histologic examination. The interval between treatment and death ranged between 7 and 797 days. Before each experimental procedure a Procion vital dye was administered as a marking agent for continued root development. Twelve of twenty teeth treated with Dycal and seventeen of twenty teeth treated with formocresol were judged to be successful as evidenced by continued root development, absence of periapical pathoses, and the presence of noninflamed or only mildly inflamed pulps. Brown and Brenn staining showed bacteria within the pulps of the teeth that failed. All but one of the teeth in this study showed evidence of continued root development as confirmed by Procion labeling.

Animals↗

Pulp reaction to a tricalcium phosphate ceramic capping agent.

A porous form of tricalcium phosphate ceramic has been shown to stimulate new bone formation around the implant. The purpose of the present study was to evaluate this material in a powder form as a pulp-capping material. It was found difficult to cover a pulp exposure adequately with Synthos ceramic powder alone. Histologic sections showed dentinogenesis around those particles which were forced into the pulp proper, demonstrating the nonirritating potential of Synthos. Because of the bacterial infection in so many of the specimens, this study is inconclusive with respect to the use of this material as a capping agent. A similar study, employing a rubber dam to protect the exposure, is recommended.

Animals↗

Oral findings in osteogenesis imperfecta.

The dentitions of twenty-eight patients, each of whom had either an autosomal dominant or a sporadic osteogenesis imperfecta (OI) syndrome, were evaluated. The diagnosis of dentinogenesis imperfecta (DI) could be established in all seven patients with dominantly inherited OI in three families, while all eight persons with dominant OI in three other families had normal teeth. Of the thirteen remaining patients with OI, twelve had no family history of the disorder; four had DI and eight had normal teeth. One person had a family history of OI and DI. All patients with abnormal tooth wear and spontaneous tooth fractures had DI. The DMF ratio increased with age in all patients with OI type I and was higher among the patients with OI type III and DI. Class III malocclusions were found in 66% of the patients. A statistically significant high incidence of impacted first and second molars was noted.

Adolescent↗

A scanning electron microscopic study of dentin dysplasia type II in primary dentition.

Dentin dysplasia type II is a rare autosomal dominant defect which affects dentin formation in both the deciduous and the permanent dentitions. The scanning electron microscopic study performed on a primary central incisor presents some findings similar to those reported in dentinogenesis imperfecta. Because of the lack of published reports on dentin dysplasia type II, it is difficult to ascertain definitive characteristics of this dentin abnormality.

Child, Preschool↗

Immunocytochemical examination of the presence of amelogenin during the root development of rat molars.

The presence of enamel proteins, especially amelogenins, during root development has been a subject of controversy for a long time. Whereas some studies have reported the presence of enamel proteins on the root surface, others were not able to detect them at these places. Since microwave (MW) processing has been shown to improve the antigen retention in mineralised tissues, we have applied MW techniques to ultrastructurally analyse the presence of amelogenin during root formation in rat molars. Upper molar tooth germs from 12 and 13-day-old Wistar rats were fixed in 0.1% glutaraldehyde + 4% formaldehyde under MW irradiation. They were then decalcified in 4.13% EDTA, dehydrated in graded concentrations of ethanol and embedded in LR White Resin. Ultrathin sections were processed for post-embedding colloidal gold immunolabelling using a chicken egg yolk antibody against a 24 kDa rat amelogenin. Then, the grids were incubated with a rabbit anti-chicken IgG secondary antibody and with a protein A-gold complex. The immunoreactivity for 24-kDa amelogenin was detected in the cytoplasm of the epithelial diaphragm cells--the most apical portion of the Hertwig's epithelial root sheath (HERS), and in less amounts on the adjacent dental papilla extracellular matrix. Amelogenin was no longer observed at advanced stages of root dentinogenesis or later, during cementogenesis. The restricted presence of amelogenin at the early stages of root formation suggests that this protein may play a role in the differentiation of ectomesenchymal cells into root odontoblasts.

Amelogenin↗