Dental caries seen from the pulpal side: a non-traditional approach.
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Animals↗
Biomedical subjects
M Larmas
Publications and source records attributed to M Larmas.
Tooth by tooth survival analysis of dental health in girls with epilepsy.
AIM: The aim of this study was to analyse, tooth by tooth, the timing of caries attacks leading to dental restoration in girls with epilepsy. STUDY DESIGN: The series comprised 60 girls with epilepsy, 8-18 years old, treated in the Departments of Paediatrics or Neurology of the Oulu University Hospital. A group of healthy age matched girls served as control. METHODS: A tooth by tooth survival analysis of the time between tooth eruption and caries attacks to a stage leading to the restorations of the permanent teeth was conducted retrospectively using data from the dental health records with annual examinations. RESULTS: The rate of dental restorations placed due to caries was constantly higher in the girls with epilepsy than in their controls. STATISTICS: The difference was significant between the first molars (p=<0.03), second molars (p=<0.02) and central incisors (p=<0.02) in the maxilla. CONCLUSION: The present observation supports the hypothesis that factors related to epilepsy, the antiepileptic medication in particular, might increase the risk of caries.
Adolescent↗
Regulation and interactions of MT1-MMP and MMP-20 in human odontoblasts and pulp tissue in vitro.
MT1-MMP is a cell-membrane-bound metalloenzyme that activates other proMMPs such as proMMP-2 and -13. We studied MT1-MMP expression in mature human odontoblasts and pulp tissue, the regulation of MT1-MMP expression by growth factors TGF-beta1 and BMP-2, and the activation of odontoblast-derived MMP-20 by MT1-MMP. MT1-MMP mRNA is expressed by native and cultured mature human odontoblasts and pulp tissue. Western blot analysis of human odontoblasts and pulp tissue detects 65- and 51-kDa pro- and active forms of MT1-MMP, and smaller truncated MT1-MMP forms. BMP-2 down-regulates MT1-MMP expression in odontoblasts and pulp tissue, while TGF-beta1, alone or with BMP-2, decreases MT1-MMP mRNA levels only slightly. We also demonstrate that MT1-MMP is capable of converting proMMP-20 into a form corresponding to the active MMP-20. In conclusion, this study demonstrates the expression and differential regulation of MT1-MMP in human dentin-pulp complex cells, and the activation of MMP-20 by MT1-MMP.
Adolescent↗
The effect of a high-sucrose diet on dentin formation and dental caries in hyperinsulinemic rats.
A high-sucrose diet decreases dentin formation and its minerals, but the mechanisms behind the effect are largely unknown. We studied the combined and separate effects of sucrose and insulin on dentin formation and mineral metabolism in growing rats. At weaning, animals were randomized into 4 groups: control/sucrose diets both with and without external insulin (1 U/x 100 g body weight daily). After 4 weeks, we measured areas of dentin formation, numbers and areas of dentinal caries lesions, and serum and urine glucose, insulin, Ca, Na, K, and P. Exogenous insulin increased serum and urine insulin levels and decreased serum glucose level, but did not affect dentin formation or dentinal caries lesion formation or progression. A high-sucrose diet decreased dentin formation independently of insulin. The differences in serum and urine minerals between the groups were minor. The findings confirm that sucrose-diet-induced reduction in dentinogenesis is independent of insulin and loss of minerals in urine.
Analysis of Variance↗
The localization of matrix metalloproteinase-20 (MMP-20, enamelysin) in mature human teeth.
MMP-20 (enamelysin), the matrix metalloproteinase family member discovered in the enamel organ, has also been detected in odontoblasts during dentin formation. We studied the presence and localization of MMP-20 in mature human teeth in health and disease. In immunohistochemistry, MMP-20-positive staining was observed most intensively in the radicular odontoblastic layer and also in dilated dentinal tubuli of caries lesions. By Western blotting, MMP-20 was detected in odontoblasts and pulp tissue of both sound and carious teeth, in dentinal fluid and dentin of sound teeth, but not in soft carious dentin. We conclude that MMP-20 produced during primary dentinogenesis is incorporated into dentin and may be released during caries progression. The main cellular source of MMP-20 in the dentin-pulp complex is the odontoblasts, which secrete MMP-20 into the dentinal fluid.
Blotting, Western↗
High-sucrose diet reduces defensive reactions of the pulpo-dentinal complex to dentinal caries in young rats.
The significance of systemic dietary effects on the response of the pulpo-dentinal complex to dentinal caries was examined. Weanling rats were divided into high sucrose or control diet groups both with and without cariogenic bacterial inoculation. At the onset, tetracycline was injected to mark the dentin formation during the experiment. After 5-6 week, mandibular molars were sectioned sagittally. The areas of dentin formed during the experiment and those of dentinal caries were quantified separately in the first and second molars. In the control diet groups the area of dentin was significantly greater under carious fissures, whereas in the high sucrose diet groups the area of dentin formed did not differ between intact and carious fissures. The high sucrose diet resulted in a significantly smaller area of dentin formation than did the control diet. The high sucrose diet with cariogenic bacterial inoculation resulted in the greatest area of dentinal caries. With the control diet a positive response against dentinal caries occurs, but the high dietary sucrose content impairs the defensive reactions of pulpo-dentinal complex against dentinal caries. These findings add further evidence of the importance of the local endogenous factors of caries progression.
Analysis of Variance↗
The effects of MMP inhibitors on human salivary MMP activity and caries progression in rats.
Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis. To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity assay with 125I-labeled gelatin as a substrate. To address the role of MMPs in the progression of fissure caries in vivo, we administered the MMP inhibitors CMT-3 and zoledronate to young rats per os for 7 weeks, 5 days a week. Caries lesions were visualized by Schiff reagent in sagittally sectioned mandibular molars. Marked reduction in gelatinolytic activity of human salivary MMPs was observed with CMT-3. CMT-3 and zoledronate, both alone and in combination, also reduced dentin caries progression in the rats. These results suggest that MMPs have an important role in dentin caries pathogenesis, and that MMP inhibitors may prove to be useful in the prevention of caries progression.
Analysis of Variance↗
Human odontoblast culture method: the expression of collagen and matrix metalloproteinases (MMPs).
Studies on mature human odontoblasts have suffered for the lack of in vitro models. We recently introduced a human odontoblast and pulp tissue organ culture method, in which the odontoblasts are cultured in the pulp chamber after removal of the pulp tissue, and the pulp tissue can be cultured separately (Tjäderhane et al., 1998a). With this method, we have studied the effects of growth factors on the expression of collagen and extracellular matrix (ECM)-degrading enzymes, matrix metalloproteinases (MMPs), in mature human odontoblasts. TGF-beta 1 was selected because of its ability to regulate the response of the dentin-pulp complex to external irritation. The effect of TGF-beta 1 (10 ng/mL) on pro alpha 1(I) collagen mRNA was analyzed by quantitative PCR, and type I procollagen propeptide (PINP) was analyzed from conditioned culture media with RIA. Odontoblast media were also assayed for respective type III procollagen propeptide (PIIINP). TGF-beta had a negligible effect on collagen mRNA expression or protein synthesis, indicating that TGF-beta alone does not markedly induce dentin matrix formation per se in the human dentin-pulp complex (Palosaari et al., 2001). However, TGF-beta 1 seems to regulate MMP expression in mature human odontoblasts differentially. A strong down-regulation of MMP-8 (Palosaari et al., 2000), a modest down-regulation of MMP-20 (Tjäderhane et al., 2000), and considerable up-regulation of MMP-9, with no apparent effect on MMP-2 expression (Tjäderhane et al., 1998b), indicate that growth factors may affect the matrix synthesis by controlling the expression and activity of MMPs instead of collagen synthesis. The altered expression of MMPs may result in altered ECM formation, which in turn may contribute to the formation of atubular reparative dentin.
Biomarkers↗
Odontoblast function seen as the response of dentinal tissue to dental caries.
Microbes are responsible for the initiation and maintaining of carious processes. They have an efficient machinery for dissolving crystalline hydroxyapatite. When initiating carious processes, microbial acid formation determines the rate of the process in enamel. When the process reaches dentin, the micro-environment changes. Dential fluid in dentin tubules is the liquid where dissolving products of apatites are destroyed. Inorganic composition of dentinal fluid, however, is not altered much during the carious process, indicating that a functional secretory domain is working to pump the dissolved calcium and phosphate ions out of the fluid. Activation of odontoblast alkaline phosphatase and dentin latent collagenases is the known cellular event during the carious process in dentin. Because the caries lesion is by definition undermining, this suggests that, in this degradation process, the extracellular compartment, crystalline hydroxyapatite is dissolved by microbial acids, and a mixture of proteinases degrades the organic matrix. The degradation products of collagen and other matrix components in dentinal fluid must be transported either through the caries lesion in the enamel to saliva or through the odontoblast to the pulp (active transport). This facilitates further processing of the degradation products intracellularly during the passage through the cell.
Alkaline Phosphatase↗
The effects of high levels of glucose and insulin on type I collagen synthesis in mature human odontoblasts and pulp tissue in vitro.
High levels of dietary sucrose affect the metabolism of the pulp-dentin complex and enhance the caries process in dentin. The high-sucrose diet reduces dentin formation in young rats (Tjäderhane et al., 1994; Hietala and Larmas, 1995; Tjäderhane, 1996) and in pups of rat dams fed high-sucrose diet during lactation (Pekkala et al., 2000a). However, the mechanisms behind the effects are unknown. A direct effect of elevated blood glucose or an indirect effect via insulin has been suggested. We investigated the effects of high glucose and insulin on type I collagen synthesis in human odontoblasts and pulp tissue in vitro, using an organ culture method for functional post-mitotic odontoblasts. Odontoblasts and pulp tissue were cultured separately for 10 days in DMEM with 15% FBS containing additional glucose (G) (4.45 g/L) or insulin (I) (0.6 microgram/mL) or both together (GI). We evaluated type I collagen synthesis with RIA, measuring the level of N-terminal propeptide of type I collagen (PINP) secreted into the culture media. PINP secretion decreased in odontoblasts and pulp tissue in G and GI groups when compared with the control and insulin samples (p = 0.001 in both groups in the pulp samples). Insulin alone did not affect PINP secretion distinctly. The results indicate that high levels of glucose, but not insulin, directly down-regulate the type I collagen synthesis in young, differentiated human odontoblasts and pulp tissue. Insulin does not affect the inhibitory effect of high sucrose. These in vitro findings indicate that the high-sucrose diet may alter odontoblast function independently of insulin.
Adolescent↗
Baseline expression and effect of TGF-beta 1 on type I and III collagen mRNA and protein synthesis in human odontoblasts and pulp cells in vitro.
Since growth factors have been suggested to regulate dentin collagen formation in response to external irritation, we investigated the effect of TGF-beta 1 on pro alpha 1 (I) collagen mRNA expression in cultured mature human odontoblasts and pulpal fibroblasts, as well as cultured human pulp tissue, using quantitative PCR. Cultured gingival fibroblasts (GF) and osteoblasts (OB) served as controls. Also, type I collagen synthesis in cultured odontoblasts and pulp tissue, as well as type III collagen synthesis in odontoblasts, were studied by measuring respective procollagen (PINP and PIIINP) secretion into culture media with radio-immunoassay (RIA). Odontoblasts expressed significantly higher basic level of type I collagen mRNA than pulp tissue or pulp fibroblasts in culture, but markedly lower level than GF and OB cells. TGF-beta 1 (10 ng/ml) had negligible effects on type I collagen mRNA expression or PINP synthesis in cultured odontoblasts and pulp tissue, and PIIINP synthesis in the odontoblasts. In PF cells, the effect of TGF-beta 1 depended on culturing conditions; a 6-fold increase in mRNA expression was observed using serum-free medium but no effect was seen in the cells cultured with 10% FBS. In contrast, GF cells serving as controls were not markedly affected by the culture conditions, with 2-3-fold increase in mRNA expression by TGF-beta 1. These experiments demonstrate that mature human odontoblasts are capable of synthesizing type III collagen protein, and that TGF-beta 1 has negligible effect on mature human odontoblast and pulp tissue collagen expression.
Adolescent↗
The reducing effects of a calcium-deficient diet and high sucrose diet on dentin apposition of rat molars.
A high sucrose diet reduces dentin apposition of growing rats. The mechanisms of reduction are unclear, but disturbances in calcium balance or in mineralization of predentin may explain them. In this experiment, 29 Sprague-Dawley rats, 21 days old, were weaned and randomized into calcium-deficient, high-sucrose or standard-diet groups for 3 weeks. They were given food and water ad libitum. During the experiment, animals were individually housed in metabolic cages where urine samples were collected. At ages of 21 and 40 days mineralizing dentin was marked using I.P. injections of oxytetracycline hydrochloride. At 42 days of age, the animals were anesthetized and their blood was collected by cardiac puncture. Right hemimandibles were sectioned sagittally and left hemimandibles were fixed, decalcified, and cut into histological sections. Dentin appositions were measured planimetrically, predentin width, from histological sections. Ca, K, and Na levels of serum and urine were measured flame photimetrically and P levels were measured by the UV method. Statistical analyses were done using one-way analysis of variation (ANOVA) Tuckey's HSD t test. In the calcium-deficient group, hypocalcemia, reduced dentin apposition, and increased predentin width were noticed when compared with the control group (P<0.05). Also, the increase in predentin width, caused by calcium deficiency, was significant compared with sucrose-fed animals (P<0.05). Sucrose diet reduced dentinogenesis, increased Ca excretion to urine, but also reduced urinary levels of P, K, and Na, and the differences were significant for the controls (P<0.05). In conclusion, despite the same kind of reduced dentinogenesis in calcium-deficient and high-sucrose groups, calcium imbalance or reduced mineralization of predentin does not explain reduced dentinogenesis in sucrose-fed animals.
Animals↗
The effect of sucrose diet of rat dams on the dentine apposition and dental caries of their pups.
The purpose was to examine whether a sucrose diet in rat dams reduces dentine apposition and enhances dental caries in their pups. Sprague-Dawley rat pups were randomized into four groups on the day of birth. During the lactation period three dams received a standard rodent diet and three a diet containing 41% sucrose. At the age of 3 weeks the pups were weaned and given an intraperitoneal injection of oxytetracycline hydrochloride. During the experimental period, half of the pups of control dams received a sucrose diet (Cnt-Suc pups) and half of the pups of sucrose dams received a standard diet (Suc-Cnt pups). The pups in the other halves received the same diet as given to their dams during lactation (Cnt-Cnt and Suc-Suc pups). Urine samples were collected from dams and pups during the test periods. After 4 weeks the pups were killed, their blood was collected and their jaws sectioned sagittally. Dentine apposition was determined planimetrically and dental caries using Schiffs staining. Ca, K and Na of serum and urine were measured flame photometrically and P using an ultraviolet method. The lactational sucrose diet was associated with decreased P and Na excretion in the dams, and also with reduced dentine apposition in their pups. Reduced dentine apposition and induced Ca excretion with decreased P, K and Na excretions were observed in Suc-Suc pups and Cnt-Suc pups during the experiment period. Fewer intact teeth with more enamel and dentinal caries lesions occurred in sucrose-exposed groups (Suc-Cnt, Cnt-Suc and Suc-Suc pups). It was concluded that the sucrose diet given to dams during lactation changed the function of the pulp dentine complex of their pups leading to reduced dentinogenesis, but also predisposed to a reduction of dentinogenesis in pups during the experimental period and enhanced the occurrence of dental caries.
Analysis of Variance↗
Effects of a high sucrose diet and intragastric sucrose feeding on the dentinogenesis, dental caries, and mineral excretion of the young rat.
Previous studies show that a high sucrose diet reduces the rate of primary dentinogenesis and increases dental caries, although their cause-effect relationship is still obscure. The purpose of this study was to explore whether the effect of sucrose load on the dentinogenesis and dental caries of young rat molars is mediated by systemic (intragastric) or by systemic and local (dietary) factors. At weaning (19 days), animals were randomized into the control, intragastric sucrose, and dietary sucrose groups for 4 weeks. The areas of dentin appositions and dentinal caries lesions were measured planimetrically. Caries was also determined with Shiffs staining and the width of predentin by histology. Urinary Ca, K, and Na levels were measured by flame photometry, urinary P levels using an UV method, and serum insulin levels using radioimmunoassay. Systemic and local sucrose load reduced dentin appositions and intragastric sucrose increased urinary Ca excretion. No differences in the width of predentin were noticed. Only dietary sucrose enhanced the occurrence and progression of caries. The present findings show that sucrose load reduces dentinogenesis by impairing the synthesis of dentin matrix, but also point out the crucial importance of the local sucrose challenge in the initiation of dental caries.
Analysis of Variance↗
The expression of MMP-8 in human odontoblasts and dental pulp cells is down-regulated by TGF-beta1.
Recent findings show that matrix metalloproteinase-8 (MMP-8) is expressed, in addition to neutrophils, by human chondrocytes, cultured fibroblasts, and endothelial cells. We investigated the expression of MMP-8 in other human mesenchyme-derived cells, odontoblasts, and pulp tissue. Odontoblasts and pulp tissue were collected from extracted human teeth for MMP-8 mRNA analysis with reverse-transcription/polymerase chain-reaction (RT-PCR) and Southern blot. The expression, localization, and secretion of MMP-8 protein were studied with Western blot, immunohistochemistry, and immunofluorometric assay. The effect of TGF-beta1 (10 ng/mL) on the expression, secretion, and concentration of secreted MMP-8 was studied by odontoblast and pulp tissue culture methods (Tjäderhane et al., 1998a). RT-PCR demonstrated MMP-8 mRNA expression in native and cultured odontoblasts and pulp tissue and cultured pulp fibroblasts, with a 522-bp transcript comparable with that of bone marrow cells. The specificity of PCR was confirmed with Southern blot. Western blot with MMP-8-specific antibody detected 65- and 50-kDa proteins in native samples, representing latent and active forms of mesenchymal-type MMP-8, and in the conditioned odontoblast culture media, 50-kDa protein was observed. TGF-beta down-regulated the MMP-8 mRNA and concentration of secreted protein in both cultures. Immunohistochemical staining detected MMP-8 in odontoblasts. These findings indicate that mesenchyme-derived cells of the dentin-pulp complex express, synthesize, and activate MMP-8, which may, in concert with odontoblast-derived gelatinases, participate in organization of dentin organic matrix prior to mineralization.
Blotting, Southern↗
Children were guaranteed regular check ups in dental study.
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Chewing Gum↗
The effect of MMP inhibitor metastat on fissure caries progression in rats.
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Animals↗
An electron probe x-ray microanalytical study of dentine minerals in sucrose-fed or glucocorticoid-medicated rats.
A high sucrose diet and glucocorticoid medication reduced dentine formation in molars of growing rats. This study was undertaken to determine whether the treatment schedules could have produced commensurate reductions in dentine minerals, and the particular concentrations of calcium (Ca) and phosphorus (P). Forty Spraque-Dawley rats were weaned at the age of 3 weeks. Tetracycline was injected i.p. to produce a fluorescent line which demarcated the preweaning from the postweaning dentine. The animals were then divided into two groups. Control rats were fed a commercial rat chow, test animals were fed a 43% sucrose diet. Half the animals in each group were also subjected to surgical implantation (s.c.) of cortisone pellets which released 0.42 mg into the circulation over a 24-hour period. At the end of the 6 week trials rats were killed and the mandibles were defleshed and prepared for electron probe microanalyzer. Each animal served as its own control, as the content of Ca, P, and total minerals were analyzed in the pre- and postweaning regions of dentine. During the preweaning there were no differences between the groups in any minerals. There was a slight reduction of minerals during the postweaning compared with the preweaning. During the postweaning, the sucrose diet significantly reduced the amount of Ca, P, and total minerals compared with the preweaning. During the postweaning, the sucrose diet reduced Ca compared with glucocorticoid medication and total minerals compared with other groups. On the contrary glucocorticoid medication seemed to compensate the reduction of minerals induced by the sucrose diet.
Animals↗