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PDGFR-alpha signaling is critical for tooth cusp and palate morphogenesis.

Platelet-derived growth factor receptor alpha (PDGFR-alpha) and PDGF ligands are key regulators for embryonic development. Although Pdgfralpha is spatially expressed in the cranial neural crest (CNC)-derived odontogenic mesenchyme, mice deficient for Pdgfralpha are embryonic lethal, making it impossible to investigate the functional significance of PDGF signaling in regulating the fate of CNC cells during tooth morphogenesis. Taking advantage of the kidney capsule assay, we investigated the biological function of PDGF signaling in regulating tooth morphogenesis. Pdgfralpha and Pdgfa are specifically and consistently expressed in the CNC-derived odontogenic mesenchyme and the dental epithelium, respectively, throughout all stages of tooth development, suggesting a paracrine function of PDGF signaling in regulating tooth morphogenesis. Highly concentrated expression patterns of Pdgfralpha and Pdgfa are associated with the developing dental cusp, suggesting possible functional importance of PDGF signaling in regulating cusp formation. Loss of the Pdgfralpha gene does not affect proper odontoblasts proliferation and differentiation in the CNC-derived odontogenic mesenchyme but perturbs the formation of extracellular matrix and the organization of odontoblast cells at the forming cusp area, resulting in dental cusp growth defect. Pdgfralpha-/- mice have complete cleft palate. We show that the cleft palate in Pdgfralpha mutant mice results from an extracellular matrix defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Collectively, our data suggests that PDGFRalpha and PDGFA are critical regulators for the continued epithelial-mesenchymal interaction during tooth and palate morphogenesis. Disruption of PDGFRalpha signaling disturbs the growth of dental cusp and interferes with the critical extension of palatal shelf during craniofacial development.

Animals↗

Association of the OGG1 Ser326Cys polymorphism with tooth loss.

Although tooth loss is a serious health problem for elderly people, little is known about the genetic basis for susceptibility to it. In the present study we aimed to find a single nucleotide polymorphism (SNP) associated with tooth loss. DNA samples from 119 outpatients (mean age=78.8 years) were genotyped on seven polymorphisms (tumor necrosis factor-alpha -1031T/C, interleukin-1beta -511C/T, interleukin-6 -634C/G, macrophage migration inhibitory factor -173G/C, interleukin-1 receptor antagonist variable number of tandem repeat in intron 2, matrix metalloproteinase-1 -16071G/2G, and oxoguanine glycosylase 1 (OGG1) Ser326Cys (1245C/G)), and the results were statistically evaluated. Of the seven polymorphisms tested, only OGG1 Ser326Cys was revealed to associate with tooth loss at a statistically significant level (P=0.0086). In addition, a multivariate logistic regression analysis in which age, gender, body mass index (BMI), and ischemic heart disease were included as independent variables indicated that Ser326Cys could be an independent factor affecting tooth loss (OR, 3.191; 95%CI, 1.174-8.672). The data suggest that the OGG1 Ser326Cys polymorphism may be associated with tooth loss.

Aged↗

Developmental mechanisms underlying tooth patterning in continuously replacing osteichthyan dentitions.

The dentition of osteichthyans presents an astonishing diversity with regard to the distribution of teeth in the oral cavity, tooth numbers, arrangements, shapes, and sizes. Taking examples from three unrelated teleosts--the most speciose group of osteichthyans--and from the literature, this study explores how the initial tooth pattern is set up, and how this relates to the establishment and maintenance (or modification) of the tooth replacement pattern. In teleosts, first-generation teeth (the very first teeth in ontogeny to develop at a particular locus) are commonly initiated in adjacent or in alternate (odd and even) positions. The mechanisms responsible for these divergent developmental patterns remain to be elucidated, in particular, whether they reflect a field or local type of control. However, patterns of adjacent or alternate tooth initiation, set up by the first-generation teeth, can easily turn into replacement patterns where new teeth are initiated simultaneously every second, or even every third position, by synchronizing the formation of new first-generation teeth to the formation of replacement teeth at older loci. Our observations suggest that, once established, the replacement pattern appears to be maintained, as a kind of "default" state. Variations and modifications in this pattern are nevertheless common and suggest that tooth replacement is under local control, exerted at the level of the initiation of replacement teeth. Further studies are needed to test the hypothesis that regular replacement patterns are more frequent in association with the plesiomorphic condition of extramedullary replacement (replacement on the surface of the dentigerous bone) and more rare in the derived condition of intramedullary replacement (replacement within the medullary cavity of the dentigerous bone).

Animals↗

Decalcified tooth matrix powder induces new bone formation and hematopoietic microenvironment in the mouse.

Implants of bone and tooth matrix powder were placed subcutaneously (s.c.) on intraperitoneal (i.p.) Mitex or Polyvic membranes. Implants were removed for histology after 1-24 weeks. Macrophages, fibroblasts, and vascular sinusoids infiltrated around bone and tooth matrix particles after one week. In the s.c. tooth matrix implants, a few sites of cartilage formation and ossification developed at two weeks, and by three weeks granulocytopoiesis and megakaryocytopoiesis developed adjacent to new bone; erythropoiesis was not observed. In s.c. bone matrix implants and in the i.p. artificial membranes coated with bone or tooth matrix powder, ossification or hematopoiesis was not observed. Small numbers of CFU-s, CFU-nm, BFU-e, and CFU-e appeared 10-20 days after s.c. implantation of tooth matrix; none were detected in s.c. bone matrix implants.

Animals↗

Specific transforming growth factor-beta subtypes regulate embryonic mouse Meckel's cartilage and tooth development.

Members of the transforming growth factor-beta (TGF-beta) superfamily have emerged as critical regulators for cell growth and differentiation. Whereas the different TGF-beta subtypes are equipotent in the majority of biological assays using cell lines cultured in vitro, there are indications that in more complex systems involving epithelial-mesenchymal interactions, the TGF-beta subtypes differ in their biological activities. To test the hypothesis that TGF-beta subtypes specifically regulate either Meckel's cartilage or tooth morphogenesis, we designed experiments to compare loss of function effects of TGF-beta 1, TGF-beta 2, and TGF-beta 3 subtypes using a serumless, chemically defined medium to culture embryonic mouse E10 (42-44 somite pairs) mandibular explants. The major effect of loss of function resulting from abrogation of TGF-beta 1 using antisense treatment resulted in a 20% increase (P < 0.05) in chondrocyte number, a decrease in extracellular matrix, and dysmorphology of the rostral region of Meckel's cartilage. Exogenous TGF-beta 1 provided indistinguishable recovery to the normal phenotype. TGF-beta 2 antisense treatment produced a threefold enlargement (P < 0.05) of tooth organs and advanced their development to the cap stage. TGF-beta 2 provided recovery to the normal phenotype (e.g., reduced tooth size and development to the bud stage), whereas TGF-beta 1 or TGF-beta 3 polypeptides had no effect. TGF-beta 3 antisense treatment resulted in a reduction of approximately 15% in the length of Meckel's cartilage. We interpret these results to suggest that TGF-beta 1 functions to regulate the number of chondrogenic cells, the amount of extracellular matrix, and the rate of developmental assembly of the rostral to posterior segments in forming Meckel's cartilage. TGF-beta 2 appears to regulate tooth size and stage of development without affecting cartilage. TGF-beta 3 appears to regulate Meckel's cartilage size without altering tooth size or shape. The results are discussed in terms of the regulatory functions of the TGF-beta subtypes during embryonic craniofacial morphogenesis.

Animals↗

Analysis of epithelial-mesenchymal interactions in the initial morphogenesis of the mammalian tooth.

Epithelial-mesenchymal interactions govern the development of epidermal organs such as teeth. During the early stages of tooth development, a local ectodermal thickening which expresses several signaling molecules appears. It is believed that these in turn signal to the underlying mesenchyme triggering mesenchymal condensation and tooth development. For example, epithelially expressed Bmp4 induces Msx1 and Lef1 as well as itself in the underlying mesenchyme. In this paper we have investigated the role of four epithelial signaling molecules, Bmp2, Shh, Wnt10a, and Wnt10b, in the early inductive cascades that govern tooth development. We show that all four genes are specifically expressed in the epithelium between E11.0 and E12.0 when tooth morphogenesis is first apparent. Although Shh, Bmp2, and Wnt10b have similar, if not identical, expression patterns, each signal has a distinct molecular action on the jaw mesenchyme. Whereas Shh and Wnt10b can induce general Hedgehog and Wnt targets, Ptc and Gli for Shh and Lef1 for Wnt10b, only Bmp2 is able to induce tooth-specific expression of Msx1. Thus, there are distinct targets for all three pathways. Interestingly, both Bmp and Wnt signaling activate Lef1, making it a candidate for integrating the two distinct signaling pathways.

3T3 Cells↗

Arrest of rat molar tooth development by lactational exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The interference with tooth development by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was studied in dioxin-resistant Han/Wistar rats. Lactating dams were given a single dose of 50 or 1000 microg TCDD/kg body wt 1 day after delivery and the pup heads were analyzed radiographically or histologically at postnatal days 9 and/or 22. Of 19 animals studied histologically, 10 lacked one or more third molars, which were at the bud stage at the start of the experiment. A higher proportion of pups exposed to the higher dose (9/13) lacked third molars than those exposed to the lower dose (1/6) (27/52 and 2/24 teeth missing, respectively). Missing upper third molars (19/38) were more frequent than were lower (10/38). The development of the third molars present was retarded. The root tips of the more advanced first and second molars were prematurely closed and root formation was arrested, but eruption was not affected. Dentinogenesis of the continuously erupting lower incisor teeth was preeruptively arrested because of pulpal cell death. All the teeth of the control rat pups developed normally. In contrast to the control pups, none of the 11 experimental pups examined radiographically (6 exposed to the higher dose and 5 to the lower) showed mineralization of their third molar cusps. The results show that the effects of TCDD on rat tooth development depend on not only the dose but also the tooth type and developmental stage. Inasmuch as early tooth development is under the control of inductive interactions between the epithelium and the mesenchyme, the interference by TCDD with tooth morphogenesis with the consequent arrest of development is likely to involve epithelial-mesenchymal signaling.

Animals↗

A modification of tooth germ cultivation in vitro and in ovo.

Mandibular molar anlages excised from 17-day mouse foetuses were cultured in vitro or in ovo (on the chorioallantoic membrane). In both cases, the explants were underlain either with a Millipore filter or with a piece of fibrin foam. Tooth germs were harvested after 7 days of cultivation and processed histologically. Spatial arrangement was highly preserved in the tooth germs cultured in vitro on fibrin foam. In vitro cultures on Millipore filters revealed significant flattening of tooth germs, caused especially by the collapse of enamel organ and the pulp. The cytodifferentiation of tooth germs cultured in vitro on both substrates (Millipore filter, fibrin foam) was characterized by the presence of odontoblasts, polarizing ameloblasts and predentine. The cytodifferentiation of tooth germs cultured in ovo on Millipore filters placed on chorioallantoic membrane was characterized by the presence of odontoblasts, ameloblasts, predentine, dentine and enamel. However, the flattening of these explants was identical with the changes of the explants cultured on Millipore filters in vitro. In ovo cultivation on the fibrin foam failed to bring satisfactory results.

Ameloblasts↗

Immunohistochemical localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp.

The distribution in oral tissues of endothelin, a multifunctional peptide originally identified within endothelial cells, and subsequently in some epithelial cells, neurons and neuroendocrine cells, has not been investigated yet. We have studied the localization of endothelin-like immunoreactivity in human tooth germ and mature dental pulp by immunohistochemical techniques. Such immunoreactivity was detected only within endothelial cells in both mature dental pulp and developing tooth. Arteries and veins of various sizes as well as small thin vessels displayed endothelin-like immunoreactivity. In the tooth germ, the cells of the enamel organ or the precursors of the odontoblasts were found unreactive. In the mature pulp, no cells of the stroma or nerves displayed endothelin-like immunoreactivity. These findings suggest that vascular endothelium may be the only source of endothelin in human dental tissues. It is tentatively proposed that endothelin released in mature tooth pulp may participate in the regulation of the pulpal blood flow. Although the possible role of endothelin in developing tissues is far from being clear, the mitogenic effects and the proto-oncogenes expression induced by endothelin in some cells raise the possibility that this peptide might also play a role during tooth development.

Adult↗

Characteristics of the tooth pulp-driven neurons in a functional column of the cat's somatosensory cortex (SI).

The columnar arrangement of tooth pulp-driven (TPD) neurons in the first somatosensory cortex (SI) was studied by single unit analysis in the cat anesthetized with nitrous oxide and halothane. Tactile sensitive neurons in the oral area of SI were arranged functionally in a columnar organization. About 32% of the recorded neurons also responded to tooth pulp stimulation. Thus, the TPD neurons located in area 3b seem to be multireceptive in sensory modality. About 80% of the TPD neurons were F-type which respond with a short latency to tooth pulp stimulation and receive input from a small number of teeth. When a microelectrode penetrated through a single vertical column, most of the F-type TPD neurons encountered received common input from one or two tooth pulps. However, when an electrode was inserted across more than one column, there was no common pulpal input to the TPD neurons encountered in a track. Thus, the TPD neurons in a single column had identical peripheral and pulpal receptive fields, and the same latency of responses to tooth pulp stimulation. These characteristics would support the hypothesis that TPD (presumed nociceptive) neurons are arranged in a vertical column and it may be inferred that the columnar organization of TPD neurons in SI plays an important role in the sensory-discriminative aspects of pulpal pain.

Afferent Pathways↗

Increased risk of tooth loss is related to bone loss at the whole body, hip, and spine.

Increased systemic bone loss may be a risk factor for tooth loss by contributing to the resorption of tooth-supporting alveolar bone. Concurrent longitudinal associations between tooth loss and bone loss at the whole body, femoral neck, and spine were examined in 189 healthy, white, dentate, postmenopausal women who participated in three intervention trials conducted within a 7-year period. None of the subjects was taking estrogen. Bone mineral density (BMD) was measured by dual photon or dual energy X-ray absorptiometry. Teeth were counted at baseline; number and timing of teeth lost over the observation period were assessed by questionnaire. All analyses were controlled for years since menopause, body mass index, number of teeth at baseline, smoking status, and the assigned treatment during each study. These interventions were calcium (Ca) or placebo (P) in Study I, vitamin D+Ca or P+Ca in Study II, and 1 of 2 doses of vitamin D+Ca in Study III. Age at baseline (mean +/- SD) was 59 +/- 6 years and the number of teeth remaining was 23 +/- 7. Women who lost teeth during the 7-year follow-up (n = 45) experienced less favorable changes in BMD at all sites compared with 144 women who lost no teeth (whole body mean +/- SE, -0.35 +/- 0.08%/year versus -0.11 +/- 0.05, P < 0.01; femoral neck -0.48 +/- 0.38%/year versus -0.14 +/- 0.35, P < 0.05; and spine, +0.05 +/- 0.21%/year versus +0. 45 +/- 0.16, P < 0.05). For each 1%/year decrement in BMD, relative risks (and 95% CI) of losing a tooth were significantly elevated at the whole body (RR = relative risks, CI = confidence interval) (RR = 4.83, CI = 1.72-13.52, n = 180), femoral neck (1.50, 1.02 to 2.22, n = 189), and spine (1.45, 1.00 to 2.11, n = 167). These results provide support for a role of systemic bone loss in the development of tooth loss among postmenopausal women.

Female↗

Dietary lipids, prostaglandin E2 levels, and tooth movement in alveolar bone of rats.

A previous study showed that certain dietary lipids can alter arachidonic acid concentrations in alveolar bone. Because arachidonic acid is a precursor of prostaglandin (PG) E2, which is known to play an important role in orthodontic tooth movement, the purpose of the present study was to determine the effect of dietary lipids on PGE2 levels and tooth movement. Two groups of male Sprague-Dawley rats (20/group) were fed nutritionally adequate purified diets containing 10% corn oil (group I, rich in n-6 fatty acids) or 9% ethyl ester concentrate of n-3 fatty acids + 1% corn oil (group II rich in n-3 fatty acids). After 5 weeks of feeding the diets, orthodontic force of 56 g was applied to the maxillary incisors to tip them distally. Prior to killing the rats at day 4 and 8 of orthodontic force application, tooth movement was measured by computerized image analysis. Premaxillae were dissected out free of soft tissue and incisors. The alveolar bone was frozen in liquid nitrogen, pulverized, and lipids were extracted. The concentrations of arachidonic acid and fatty acid composition of total phospholipids were measured by gas chromatography. PGE2 levels were measured by enzyme immunoassay. Arachidonic acid and PGE2 concentration were significantly lower (P < 0.001) in alveolar bone of rats in group II than in group I. The tooth movement was also significantly lower (P < 0.02) in group II than in group I at both 4 and 8 days. The results suggest that PGE2 levels in alveolar bone and orthodontic tooth movement can be affected by the type of dietary fat.

Alveolar Process↗

Application of mechanical mobility of periodontal tissues to tooth mobility examination.

Tooth mobility examination is important in planning dental treatment, as it may give an indication of alveolar bone loss and the condition of the periodontal ligament. In clinical dental diagnosis a manual tooth mobility examination is useful. However, its determination of tooth mobility is subjective and depends on the skill and experience of the clinician. The authors have previously reported on a device for measuring the biomechanical properties of human periodontium using an impedance head. Using this device, the mechanical mobility of periodontium can be measured and the mechanical parameters of the periodontal physical model are obtained. Tooth mobility is defined objectively on the basis of discriminant scores of mechanical parameters, and a mobility triangle (MT) figure is drawn as a record for visual interpretation. The paper describes the validation of the mechanical mobility measurements and their interpretation using mobility parameters and a personal computer to produce a mobility triangle figure. The method is compared favourably with clinical mobility measurement. The relationship of the model to underlying pathology is tested by measurements performed on various tooth model systems.

Biomechanical Phenomena↗

Enameloid/enamel transition through successive tooth replacements in Pleurodeles waltl (Lissamphibia, Caudata).

Study of the evolutionary enameloid/enamel transition suffers from discontinuous data in the fossil record, although a developmental enameloid/enamel transition exists in living caudates, salamanders and newts. The timing and manner in which the enameloid/enamel transition is achieved during caudate ontogeny is of great interest, because the caudate situation could reflect events that have occurred during evolution. Using light and transmission electron microscopy, we have monitored the formation of the upper tooth region in six successive teeth of a tooth family (position I) in Pleurodeles waltl from late embryos to young adult. Enameloid has only been identified in embryonic tooth I(1) and in larval teeth I(2) and I(3). A thin layer of enamel is deposited later by ameloblasts on the enameloid surface of these teeth. From post-metamorphic juvenile onwards, teeth are covered with enamel only. The collagen-rich enameloid matrix is deposited by odontoblasts, which subsequently form dentin. Enameloid, like enamel, mineralizes and then matures but ameloblast participation in enameloid matrix deposition has not been established. From tooth I(1) to tooth I(3), the enameloid matrix becomes ever more dense and increasingly comes to resemble the dentin matrix, although it is still subjected to maturation. Our data suggest the absence of an enameloid/enamel transition and, instead, the occurrence of an enameloid/dentin transition, which seems to result from a progressive slowing down of odontoblast activity. As a consequence, the ameloblasts in post-metamorphic teeth appear to synthesize the enamel matrix earlier than in larval teeth.

Animals↗

[Tooth extraction in cases of dental abscess].

BACKGROUND: Surgical relief and drainage as well as adjunct medicinal and physical therapy of dental abscesses are indisputable treatment options. It is currently controversial at what time the tooth extraction should take place. The aim of this study was to determine whether there are differences in treatment success depending on the time of tooth extraction. PATIENTS AND METHODS: A randomized patient sample (n=177) from two clinics was examined that differed in the therapy only regarding the time of tooth extraction. Post-surgical complications, inpatient care, duration of surgeries and incidents during anesthesia were examined. RESULTS: Statistically significant differences for inpatient care were impressive. done Abscess incision and tooth extraction performed simultaneously led to an average hospital stay of 8 days compared to 11 days when done at two different times. Duration of surgeries was also significantly shorter for the single procedure. Post-surgical complications only occurred in 2-4% of all cases. DISCUSSION: Opinions expressed in the literature include complete refusal to do tooth extraction immediately, or extraction of the causal teeth while providing antibiotic protection or even complete support of immediate extraction. Considering all factors, this study supports a single procedure with a shorter duration of hospital stays depending on local, personnel and logistical circumstances, especially regarding the forthcoming introduction of the DRGs.

Adult↗

Expression of genes for gelatinases and tissue inhibitors of metalloproteinases in periodontal tissues during orthodontic tooth movement.

Orthodontic tooth movement progresses by a combination of periodontal ligament (PDL) tissue and alveolar bone remodeling processes. Besides the remodeling of alveolar bone around the moving teeth, the major extracellular matrix (ECM) components of PDLs, collagens, are degenerated, degraded, and restructured. Matrix metalloproteinases (MMPs) and their specific inhibitors, tissue inhibitors of metalloproteinases (TIMPs), act in a co-ordinated fashion to regulate the remodeling of periodontal tissues. We hypothesized that the expression levels of the genes for MMP-2, MMP-9, and TIMPs 1-3 are increased transiently in the periodontal tissue during orthodontic tooth movement. To test this hypothesis, we employed an animal model of tooth movement using rats, as well as in situ hybridization to analyze the expression levels of Mmp-2, Mmp-9, and Timps 1-3. The expression levels of these genes increased transiently in cells of periodontal tissues, which include cementoblasts, fibroblasts, osteoblasts, and osteoclasts, at the compression side of the moving teeth. The transient increases in gene expression at the tension side were mainly limited to osteoblasts and cementoblasts. In conclusion, the expression levels of Mmp-2, Mmp-9, and Timps 1-3 increase transiently during orthodontic tooth movement at both the tension and compression sides. The expression of these genes is regulated differentially in the periodontal tissue of the tension side and compression side. This altered pattern of gene expression may determine the rate and extent of remodeling of the collagenous ECM in periodontal tissues during orthodontic tooth movement.

Animals↗

Understanding, planning, and managing tooth movement: orthodontic force system theory.

A simple force may cause translation and/or rotation of the tooth upon which it acts. The closer the line of force to the tooth's center of resistance, the greater is the proportion of translation relative to rotation, and vice versa. When a tooth is subjected to a tipping moment, strain is concentrated in the areas of the alveolar crest and root apex. This may explain how a light force can tip a tooth readily, while translation, involving a more even distribution of strain throughout the length of the root, requires more force with little or no moment. It is difficult to sustain a desired combination of rotational and translational movement over any significant distance. Couples induce rotation only. Couples and simple forces can be used in combinations to effect movements that are not possible with either one alone. Molars provide anchorage for incisor intrusion. This "vertical anchorage" can be reinforced by elastics producing moments opposite those produced by arch wire anchor bends. Calculation of the elastics' contribution provides an indication of the intrusive force that may be applied to incisors without reciprocal molar tipping. The common use of the term center of rotation in orthodontics may be inappropriate and/or confusing. It may be more accurate and straightforward to view most tooth movements as combinations of linear translation with rotation about the center of resistance.

Adolescent↗

Orchestration of tooth movement.

Recent advances in the art and mechanics of delivering orthodontic forces have achieved greater precision and control of tooth movement. The exact mechanism by which these forces orchestrate tooth movement is not thoroughly understood. An accurate understanding and precise control over the factors responsible for initiating and carrying out the tissue reaction will ultimately optimize the rate of tooth movement. An integrated hypothetical model for the mechanism of tooth movement is discussed here. This model is based on the most recent body of information available to explain how various stimuli affect bone cells. The roles played by piezoelectric responses, prostaglandin production, and biochemical factors are discussed, with particular emphasis on their importance and contribution in terms of maximizing the rate of tooth movement. The intelligent use of this knowledge will permit us to modify the orthodontic appliance and treatment regimen in order to achieve an optimum tissue response.

Alveolar Process↗