Bone Morphogenetic Protein 2 Coordinates Early Tooth Mineralization.

Formation of highly organized dental hard tissues is a complex process involving sequential and ordered deposition of an extracellular scaffold, followed by its mineralization. Odontoblast and ameloblast differentiation involves reciprocal and sequential epithelial-mesenchymal interactions. Similar to early tooth development, various Bmps are expressed during this process, although their functions have not been explored in detail. Here, we investigated the role of odontoblast-derived Bmp2 for tooth mineralization using Bmp2 conditional knockout mice. In developing molars, Bmp2LacZ reporter mice revealed restricted expression of Bmp2 in early polarized and functional odontoblasts while it was not expressed in mature odontoblasts. Loss of Bmp2 in neural crest cells, which includes all dental mesenchyme, caused a delay in dentin and enamel deposition. Immunohistochemistry for nestin and dentin sialoprotein (Dsp) revealed polarization defects in odontoblasts, indicative of a role for Bmp2 in odontoblast organization. Surprisingly, pSmad1/5/8, an indicator of Bmp signaling, was predominantly reduced in ameloblasts, with reduced expression of amelogenin ( Amlx), ameloblastin ( Ambn), and matrix metalloproteinase ( Mmp20). Quantitative real-time polymerase chain reaction (RT-qPCR) analysis and immunohistochemistry showed that loss of Bmp2 resulted in increased expression of the Wnt antagonists dickkopf 1 ( Dkk1) in the epithelium and sclerostin ( Sost) in mesenchyme and epithelium. Odontoblasts showed reduced Wnt signaling, which is important for odontoblast differentiation, and a strong reduction in dentin sialophosphoprotein ( Dspp) but not collagen 1 a1 ( Col1a1) expression. Mature Bmp2-deficient teeth, which were obtained by transplanting tooth germs from Bmp2-deficient embryos under a kidney capsule, showed a dentinogenesis imperfecta type II-like appearance. Micro-computed tomography and scanning electron microscopy revealed reduced dentin and enamel thickness, indistinguishable primary and secondary dentin, and deposition of ectopic osteodentin. This establishes that Bmp2 provides an early temporal, nonredundant signal for directed and organized tooth mineralization.

Age estimation in an Indian population using pulp/tooth volume ratio of mandibular canines obtained from cone beam computed tomography.

The present study assessed the suitability of pulp/tooth volume ratio of mandibular canines for age prediction in an Indian population. Volumetric reconstruction of scanned images of mandibular canines from 140 individuals (aged ten - 70 years), using computed tomography was used to measure pulp and tooth volumes. Age calculated using a formula reported earlier for a Belgian sample, resulted in errors > ten years in almost 86% of the study population. The regression equation obtained for the Indian population: Age = 57.18 + (- 413.41 x pulp/tooth volume ratio), was applied to an independent control group (n = 48), and this resulted in mean absolute errors of 8.54 years which was significantly (p < 0.05) lower than those derived with the Belgian formula. The pulp/tooth volume ratio is a useful indicator of age, although correlations may vary in different populations and hence, specific formulae should be applied for the estimates.

Genetic basis for tooth malformations: from mice to men and back again.

Teeth arise from sequential and reciprocal interactions between the oral epithelium and the cranial neural crest-derived mesenchyme. Their formation involves a precisely orchestrated series of molecular and morphogenetic events. Numerous regulatory genes that have been primarily found in organisms such as Drosophila, zebrafish, xenopus and mouse are associated with all stages of tooth formation (patterning, morphogenesis, cytodifferentiation and mineralization). Most of these genes belong to evolutionary conserved signaling pathways that regulate communication between epithelium and mesenchyme during embryonic development. These signaling molecules together with specific transcription factors constitute a unique molecular imprint for odontogenesis and contribute to the generation of teeth with various and function-specific shapes. Mutations in several genes involved in tooth formation cause developmental absence and/or defects of teeth in mice. In humans, the odontogenic molecular program is not as well known as that of mice. However, some insight can be obtained from the study of mutations in regulatory genes, which lead to tooth agenesis and/or the formation of defective dental tissues.

Biodegradation, soft and hard tissue integration of various polyethylene glycol hydrogels: a histomorphometric study in rabbits.

OBJECTIVES: (i) To evaluate biodegradation, hard and soft tissue integration using various polyethylene glycol (PEG) hydrogels; (ii) to evaluate the influence of arginine-glycine-aspartic acid (RGD) on two types of PEG hydrogels. MATERIAL AND METHODS: In seven rabbits, six treatment modalities were randomly applied subperiosteally on the skull: (1) a dense network PEG hydrogel (PEG1), (2) PEG1 modified with RGD (PEG1-RGD), (3) a looser network PEG hydrogel (PEG2), (4) PEG2 modified with RGD (PEG2-RGD), (5) a collagen membrane, and (6) a polylactide/polyglycolide/trimethylene carbonate membrane. The animals were sacrificed at 14 days. Histomorphometric analyses were performed on undecalcified Epon sections using a standardized region of interest. For statistical analysis, paired t-test and signed rank test were applied. RESULTS: PEG1 and PEG1-RGD remained intact and maintained the shape. PEG2 and PEG2-RGD completely degraded and were replaced by connective tissue and bone. The largest amount of mineralized tissue was found for PEG2-RGD (21.4%), followed by PEG 2 (9.5%). The highest percentage of residual hydrogel/membrane was observed for PEG1-RGD (55.6%), followed by PEG1 (26.7%). CONCLUSIONS: Modifications of the physico-chemical properties of PEG hydrogels and the addition of RGD influenced soft and hard tissue integration and biodegradation. PEG1 showed an increased degradation time and maintained the shape. The soft tissue integration was enhanced by adding an RGD sequence. A high turn-over rate and extensive bone regeneration was observed using PEG2. The addition of RGD further improved bone formation and soft tissue integration.

Stem cells for tooth engineering.

Tooth development results from sequential and reciprocal interactions between the oral epithelium and the underlying neural crest-derived mesenchyme. The generation of dental structures and/or entire teeth in the laboratory depends upon the manipulation of stem cells and requires a synergy of all cellular and molecular events that finally lead to the formation of tooth-specific hard tissues, dentin and enamel. Although mesenchymal stem cells from different origins have been extensively studied in their capacity to form dentin in vitro, information is not yet available concerning the use of epithelial stem cells. The odontogenic potential resides in the oral epithelium and thus epithelial stem cells are necessary for both the initiation of tooth formation and enamel matrix production. This review focuses on the different sources of stem cells that have been used for making teeth in vitro and their relative efficiency. Embryonic, post-natal or even adult stem cells were assessed and proved to possess an enormous regenerative potential, but their application in dental practice is still problematic and limited due to various parameters that are not yet under control such as the high risk of rejection, cell behaviour, long tooth eruption period, appropriate crown morphology and suitable colour. Nevertheless, the development of biological approaches for dental reconstruction using stem cells is promising and remains one of the greatest challenges in the dental field for the years to come.

Histological, ultrastructural and quantitative investigations on the response of healthy human pulps to experimental capping with mineral trioxide aggregate: a randomized controlled trial.

AIM: To investigate the pulpal response to direct pulp capping in healthy human teeth with mineral trioxide aggregate (MTA) as against calcium hydroxide cement (Dycal) as control. METHODOLOGY: Twenty healthy human third molars had iatrogenic pulpotomy and direct pulp capping with MTA. Another 13 teeth were capped with Dycal as controls. The teeth were restored, with IRM, clinically reviewed and extracted after a number of pre-determined intervals (1 week, 1 month and 3 months). The specimens were fixed, decalcified, subdivided axially into two halves in the oro-buccal (lingual-buccal) plane, embedded in plastic, serial sectioned and evaluated qualitatively and quantitatively by correlative light and transmission electron microscopy with appropriate statistical evaluation of the quantitative data. RESULTS: Iatrogenic pulpal wounds treated with MTA were mostly free from inflammation after 1 week and became covered with a compact, hard tissue barrier of steadily increasing length and thickness within 3 months following capping. Control teeth treated with Dycal revealed distinctly less consistent formation of a hard tissue barrier that had numerous tunnel defects. The presence of pulpal inflammation up to the longest observation period (3 months) after capping, was a common feature in Dycal specimens. CONCLUSIONS: The MTA was clinically easier to use as a direct pulp-capping agent and resulted in less pulpal inflammation and more predictable hard tissue barrier formation than Dycal. Therefore, MTA or equivalent products should be the material of choice for direct pulp capping procedures instead of hard setting calcium hydroxide cements.

Effect of sodium hypochlorite on human root dentine--mechanical, chemical and structural evaluation.

AIM: To investigate the mechanical, chemical and structural alterations of human root dentine following exposure to ascending sodium hypochlorite concentrations. METHODOLOGY: Three-point bending tests were carried out on standardized root dentine bars (n = 8 per group, sectioned from sound extracted human third molar teeth) to evaluate their flexural strength and modulus of elasticity after immersion in 5 mL of water (control), 1% NaOCl, 5% NaOCl or 9% NaOCl at 37 degrees C for 1 h. Additional dentine specimens were studied using microelemental analysis, light microscopy following bulk staining with basic fuchsin, and scanning electron microscopy (SEM). Numerical data were compared using one-way ANOVA. Bonferroni's correction was applied for multiple testing. RESULTS: Immersion in 1% NaOCl did not cause a significant drop in elastic modulus or flexural strength values in comparison to water, whilst immersion in 5% and 9% hypochlorite reduced these values by half (P < 0.05). Both, carbon and nitrogen contents of the specimens were significantly (P < 0.05) reduced by 5% and 9% NaOCl, whilst 1% NaOCl had no such effect. Exposure to 5% NaOCl rendered the superficial 80-100 mum of the intertubular dentine permeable to basic fuchsin. Three-dimensional SEM reconstructions of partly demineralized specimens showed NaOCl concentration-dependent matrix deterioration. Backscattered electron micrographs revealed that hypochlorite at any of the tested concentrations left the inorganic dentine components intact. CONCLUSIONS: The current data link the concentration-dependent hypochlorite effect on the mechanical dentine properties with the dissolution of organic dentine components.

A comparative study on the disinfection potentials of bioactive glass S53P4 and calcium hydroxide in contra-lateral human premolars ex vivo.

AIM: To evaluate the effects of bioactive glass S53P4 versus calcium hydroxide when used as dressings in contra-lateral human premolars infected with Enterococcus faecalis ATCC 29212. METHODOLOGY: Pairs of contra-lateral premolar teeth plus single control premolars were obtained from 23 individuals aged 10-26 years undergoing orthodontic treatment. Root canals of teeth with fully formed apices (nine contra-lateral pairs, seven controls) were instrumented using a size 60 FlexoFiles 2 mm short of canal length. Canals with open apices (six contra-lateral pairs, four controls) were circumferentially instrumented using a FlexoFile. Root canals were rinsed with 1% sodium hypochlorite and 10% citric acid. Teeth were then suspended in tryptic soy broth (TSB) and autoclaved. Positive controls and study teeth were infected with E. faecalis ATCC 29212 for 2 weeks in TSB, while negative controls were kept in sterile TSB. Subsequently, contra-lateral premolars were dressed with bioactive glass S53P4 (BAG) or calcium hydroxide suspensions for 10 days. Dentine samples were obtained from teeth with fully formed apices using ISO-size 70, 80 and 90 FlexoFiles to working length and cultured. Teeth with open apices were fixed, fractured and examined using scanning electron microscopy (SEM). RESULTS: Calcium hydroxide had a strong antibacterial effect and was significantly more effective than BAG in preventing residual bacterial growth (P < 0.01). SEM analysis revealed apparent substance-specific modes of action. CONCLUSIONS: Calcium hydroxide was an effective disinfectant in human teeth.

Tubular sclerosis rather than the smear layer impedes dye penetration into the dentine of endodontically instrumented root canals.

AIM: To evaluate the effect of different root canal irrigating regimes on dentine penetration of Patent Blue dye. METHODOLOGY: Eighty extracted single-rooted human mandibular premolar teeth with narrow root canals were prepared using ProFile instruments. After each instrument, canals were irrigated with 1% sodium hypochlorite. Subsequently, teeth were randomly assigned to receive a 10 mL rinse of aqueous 17% (w/v) ethylenediaminetetraacetic acid or tap water for 2 or 10 min, followed by a final rinse with a 2% Patent Blue dye solution for 2 or 10 min (eight groups, n = 10 teeth per group). Teeth were then horizontally sectioned 3, 6 and 9 mm from the apex. Sections were digitally photographed and dye penetration was calculated as percentage of total dentine area using NIH Image J. Values were compared using one-way anova and Bonferroni correction with the alpha-type error set at <0.05. Representative tooth sections from all groups were further analysed using scanning electron microscopy. RESULTS: No significant impact of irrigating protocols on dye penetration was found. Dye penetration was significantly (P < 0.001) greater in the coronal than middle, and in middle than in apical root thirds. When observed microscopically, irrigant penetration was independent of the presence of a smear layer, but was rather a function of tubular sclerosis. CONCLUSIONS: Tubular sclerosis, a physiological phenomenon that starts in the third decade of life in the apical root region and advances coronally with age, was the main factor influencing penetrability of root dentine.

Quantitative histological features and ultrastructure of opercula of human teeth showing normal and delayed eruption.

BACKGROUND: Failure of eruption of human permanent molars has been attributed to opercular lesions, although comparisons with specimens from normally erupting teeth are scarce. The aim of this study was to quantitatively analyse opercula associated with normal and delayed tooth eruption. METHOD: Twenty opercula covering permanent molars delayed in eruption were obtained from 13 patients aged 7.3-18.1 years. Six opercula from normally erupting molars of five 7.3-17.5-year-old subjects served as controls. Specimens were analysed light and electron microscopically and morphometrically. RESULTS: In addition to features recognized previously, prominent numbers of nerves, high endothelial-like venules and mast cells were observed. Ultrastructurally, large multinucleated cells did not reveal cell boundaries running between the nuclei, and mast cells seemed belonging to the MC(TC)-type. None of the features differed significantly between opercula from cases of delayed and normal tooth eruption. CONCLUSIONS: Disturbances of tooth eruption that are attributed to opercular lesions may represent retentions resulting from the failure of the eruption mechanism, rather than impactions because of a physical barrier.

Observations on pulpal response to carbon dioxide laser drilling of dentine in healthy human third molars.

Preservation of pulpal health is the primary prerequisite for successful application of laser systems in the hard tissue management of vital teeth. The purpose of this study was to investigate the short and long-term pulpal effects to cavity preparations in healthy human teeth using carbon dioxide (CO2) laser. A total of seven, healthy, third molars that were scheduled to be removed due to space problems were used. After the laser drilling, the occlusal cavities were closed temporarily, and the teeth were extracted 7 days (n=5) and 3 months (n=2) after the operation. The specimens were fixed, decalcified, subdivided and processed for light and transmission electron microscopy. Seven days postoperatively all the five teeth that had been irradiated with the CO2 laser did not reveal any pathological changes in the pulpo-dentine complex. Three months postoperatively the two teeth that were prepared with the laser showed subtle but distinct apposition of tertiary dentine that was lined with intact odontoblasts. One of the specimens at 3 months revealed the presence of a mild, but very circumscribed, pulpal infiltration of chronic inflammatory cells subjacent to the cavity preparation. The latter is unlikely to be due to a direct effect of the laser irradiation but a possible consequence of microleakage of oral antigens and/or other tissue-irritating molecules through the temporary restoration and the remaining dentine thickness (RDT). Although these preliminary histological results suggest that the CO2 laser under investigation induced only minimal response of the dentine-pulp complex when used as a hard-tissue drilling tool, with specific energy settings, pulse duration within thermal relaxation time and emitting radiations at 9.6 microm of wavelength, larger clinical trials involving various types of teeth are necessary to reach definite conclusions for large-scale clinical application of the laser device.

Nature and attachment of cementum formed under guided conditions in human teeth. An electron microscopic study.

In an attempt at characterizing the nature and attachment of cementum formed under conditions of guided tissue regeneration (GTR) in humans, front teeth from 4 patients aged 42 to 72 years were examined at the electron microscopic level. All teeth were affected by complex periodontitis associated with advanced loss of periodontal support. Roots were surgically planed and notched, but not chemically conditioned. Either the mesial or distal surface of each tooth represented the experimental site and was covered with a biodegradable polyglactin 910 barrier, while the opposite approximal surface served as control. Following 3 months of healing, teeth were removed together with surrounding periodontal tissues including some alveolar bone. These blocks were fixed histologically, decalcified, embedded in epoxy, and sectioned for examination in the scanning (backscatter mode) and transmission electron microscope. Both experimental and control sites disclosed 2 types of regenerative cementum that seemed to be formed by cells resembling cementoblasts. The first type was characterized by a thin fringe of collagen fibrils which were arranged perpendicular to the root surface and appeared mineralized in a zone extending about 1 to 3 microm from the dentin. The second type occurred as thick patches which revealed scattered cementocytes and sheets of collagen fibrils oriented mainly parallel to the root surface, running both circularly and axially. In both situations, a continuous, thin, electrondense layer was interposed between newly formed cementum and preexisting radicular hard tissues. Interdigitation of collagen fibrils from cementum and dentin, such as observed along the natural cemento-dentinal junction, did not occur. Thus, regenerative cementum laid down in humans under guided conditions on previously diseased and planed, but not otherwise treated root surfaces shares some morphologic features with cementum formed during spontaneous repair of root resorptions. However, unlike in the course of such repair, a fibrous attachment of new cementum resembling the natural cemento-dentinal junction does not seem to be regenerated under guided conditions.

Age changes in the articular tissue of human mandibular condyles from adolescence to old age: a semiquantitative light microscopic study.

In a previous study (Luder, Anat. Rec., 1997;248:18-28), the articular tissue of the adult mandibular condyle was characterized semiquantitatively. However, questions about age changes of mature tissue were not answered, and the time course of tissue maturation from the end of condylar growth to the attainment of the adult appearance remained unknown. These issues are addressed in the present investigation. By using a light microscope, features of the superficial, intermediate, and deep articular tissue zones as well as of the subchondral bone were assessed at nine predetermined condylar sites. The frequencies of these features were recorded as scores from 0 (absent) to 10 (continuous) and were plotted against age. Analysis of covariance served for testing the significance of age and sex effects as well as intracondylar variability. Whereas almost all age-related changes in frequencies of tissue features were similar along the whole lateromedial dimension, changes at the putatively nonload-bearing, posterior slope differed significantly from those at the putatively load-bearing, anterior slope and zenith of the condyle. Two patterns of changes were noted. Frequencies of a first group of tissue features altered mainly during the age period from 15 years to 30 years and remained more or less stable thereafter. This course was characteristic for 1) a progressive cartilaginification of the superficial zone as well as 2) the disappearance of hypertrophic growth cartilage and 3) the appearance of grid-fibrous fibrocartilage in the deep zone, which were accompanied by 4) a decline in endochondral ossification and 5) the formation of a compact, subchondral bone plate. Frequencies of a second group of tissue features disclosed changes that continued up to middle and old age. This pattern was evident regarding 1) a decrease in the prominence associated with 2) a drop in cellularity and 3) progressive fibrosis or even cartilaginification of the intermediate zone. Among the age changes of condylar articular tissue, those affecting the superficial and deep zones as well as the subchondral bone are largely complete by about 30 years of age and seem to be related primarily to a gradual transition from growth to adulthood. In contrast, a second group of alterations, which progress to old age and involve mainly the intermediate zone, appears to be associated with continued maintenance and adaptive articular remodeling as well as possibly senescence. Both maturational and later age changes seem to depend markedly on articular load bearing.

Frequency and distribution of articular tissue features in adult human mandibular condyles: a semiquantitative light microscopic study.

BACKGROUND: The adult mandibular condyle is reported to be covered by fibrocartilage that develops from growth cartilage present earlier in life. Available data on the organization of condylar fibrocartilage are entirely descriptive or have been derived from young adult individuals. In order to examine the variability in normal appearance, condyles from a representative sample of adult humans were analyzed semiquantitatively. METHODS: With a light microscope, features of the superficial, intermediate, and deep tissue zones subjacent to small contiguous sectors of the articular surface were recorded. The distribution of each feature relative to the total surface was then calculated and respective data obtained from nine predetermined condylar regions and from males and females were compared using analysis of variance. RESULTS: The organization of the articular tissue varied significantly in the anteroposterior direction only. Unlike during growth, the superficial and deep zones in anterior and superior regions mostly contained fibrocartilage, although of markedly different appearance. Furthermore, the intermediate zone along about half of its anteroposterior extension lacked a distinctly visible layer, because the cell density was low and there was dense fibrous tissue or fibrocartilage similar to that of the superficial or deep zone, respectively. In these situations, zonation of the articular tissue was revealed only by the arrangement of collagen fibers. CONCLUSIONS: The appearance of adult condylar articular tissue, in addition to varying considerably within and between putative load-bearing and nonload-bearing regions, bears only a vague resemblance to the layered organization of the growing condyle. Current terminology that refers to that organization, therefore, is inappropriate. It is proposed to designate impartially the three articular tissue zones of the adult condyle as "superficial," "intermediate," and "deep."

Mild dental findings associated with severe osteogenesis imperfecta due to a point mutation in the alpha 2(I) collagen gene demonstrate different expression of the genetic defect in bone and teeth.

Serial intraoral photographs, radiographs, and ground sections from an extracted upper permanent canine served to characterize dental abnormalities in a 15-year-old girl suffering from severe (type III) osteogenesis imperfecta (OI) due to a point mutation that substituted glycine 688 of the alpha 2(I) chain of collagen I by serine. Dental records showed that all deciduous teeth exhibited clinical and radiographic characteristics of dentinogenesis imperfecta (DI), whereas permanent teeth including the removed canine appeared normal, although pulp chambers contained unusually large denticles. Despite the unconspicuous clinical appearance of the canine, histologic sections revealed small, canal-like, hypomineralized hard tissue patches that lacked a regular tubular structure and occupied a narrow band of the bulk of normal circumpulpal dentin at about the level of the cemento-enamel junction. The finding that a mutation in the gene for the alpha 2(I) collagen chain with serious consequences in bone has only minor effects in teeth would suggest that odontoblasts, unlike osteoblasts, can largely compensate for this particular genetic defect, possibly by excluding the abnormal alpha 2(I) chains and forming alpha 1(I) homotrimeric collagen I. The discrepant consequences in deciduous as opposed to permanent teeth and the specific localization of the dentinal abnormalities in permanent teeth lead us to speculate that the exclusion of defective alpha 2(I) chains could depend on the developmental stage and/or the rate of extracellular matrix formation.

Perichondrial and endochondral components of mandibular condylar growth: morphometric and autoradiographic quantitation in rats.

In an attempt to determine the contribution of the perichondrial and endochondral components to rapid and slow overall condylar growth, mandibular condyles from rats aged 21 and 45 d as well as 3 and 6 months were examined by light microscopy. A morphometric analysis served to estimate the size of cells and the amount of extracellular matrix per cell in the various tissue layers beneath the articular surface. Quantitative evaluation of autoradiographic labelling due to the presence of [3H]-thymidine, [3H]-proline, and [35S]-sulphate 1.5 or 2 h and 5 d after injection of the tracer was used to determine the velocity of overall condylar growth. A combination of the two types of results allowed the calculation of daily rates in (1) the generation of new chondrocytes, constituting the perichondrial growth component, and the endochondral components comprising (2) net accumulation of extracellular matrix in the cartilage and (3) enlargement of the chondrocytes. It was observed that the 3 factors contributed, respectively, by about 10-25, 30 and 45-60% to rapid growth and by about 75, 15 and 10% to slow growth. Thus when growth slowed, the contribution of chondrocyte enlargement declined markedly and that of matrix accumulation slightly, while the contribution of new cell generation increased correspondingly. Declines in chondrocyte enlargement and in accumulation of cartilage matrix that was related mainly to decreasing proteoglycan formation were in good agreement with age-associated variation in weight gain, while peak rates in generation of new chondrocytes appeared to be delayed against peak somatic growth. It is concluded that (1) endochondral components contribute most to particularly rapid condylar growth, exceeding the perichondrial component, and (2) endochondral components of condylar growth are regulated by systemic factors that also control somatic growth.

Histometric study of synovial cavity dimensions of human temporomandibular joints with normal and anterior disc position.

To evaluate effects of internal derangement, the sagittal lengths of the condylar, temporal, and disc articular surfaces, as well as those of the disc attachments, were measured in histologic sections of human temporomandibular joints obtained at autopsy, mainly from adolescent, young adult, and middle-aged subjects. While the upper joint compartment appeared little affected, anterior disc position was significantly associated with comparatively long inferior disc attachments and a short condylar articular surface, indicative of possibly aberrant insertions of the attachments. Such discrepancies in size or alignment between condyle and disc complex could primarily reflect a constitutional deviation or result secondarily from remodeling.

Onset of human aging estimated from hazard functions associated with various causes of death.

In an attempt to estimate the onset of aging-associated mortality in humans, Swiss national survival and mortality data from 1978 to 1983 were analyzed. The nonparametric kernel method served to estimate gender-specific survival and hazard functions related to five major as well as all causes of death. On the basis of graphical models, it was hypothesized that the onset of aging conceivably was associated with prominent acceleration in mortality rates. The earliest maximal accelerations in hazard functions for most causes of death occurred during the second and again during the fourth age decade. Overall mortality rates of males and females exhibited prominent humps between the two periods of acceleration. These humps were accounted for largely by a high incidence of deaths from violence (accidents, suicide, and crime), which have to be attributed to environmental factors rather than to senescence. On the other hand, no plausible argument could be found against the assumption that maximal acceleration in death rates from ischemic heart and other circulatory diseases around 20 years of age was related to aging. Therefore, these data were interpreted to indicate that in the population examined, senescent mortality sets in around 20 years of age, about 5 years earlier in males than in females. However, when considering overall hazard rates, aging is hidden from view by mortality associated with environmental factors, which predominates up to ages of 30-35 years in both genders.

Articular degeneration and remodeling in human temporomandibular joints with normal and abnormal disc position.

Temporomandibular joints with normal and abnormal disc positions, obtained from 15 females and 38 males (most between 15 and 50 years of age), were examined under a light microscope. Histologic changes attributed to degeneration and remodeling of the articular tissues were graded according to their prominence and extension along the articular surfaces. These changes seemed little affected by internal derangement in the condyle and the temporal component. In contrast, degeneration and regressive remodeling of the disc and, although to a much lesser degree, its attachments were more severe and increased more steeply with age in internally deranged as compared to normal joints. The present findings suggest that the disc indeed suffers from an abnormal position. However, this conclusion seems tenable only for adults, as rather prominent progressive remodeling changes have been observed in joints from adolescents, but no significant degenerative variations were noted.