Incisor Growth Research Articles

A New Rat Model of Maxilla Allotransplantation

We developed a rat model to test the effects of vascularized maxilla allotransplantation on composite maxillary substructures. Allograft maxilla transplantations were performed across the major histocompatibility barrier between 10 Lewis-Brown-Norway (RT1(n+l)) and 10 Lewis (RT1(l)) recipient rats under cyclosporin A monotherapy. Grafts were dissected along Le-Fort II osteotomy lines based on the common carotid artery and external jugular vein and transplanted to the anterior abdominal wall via microvascular anastomosis. Allografts were examined by tomography, flow cytometry, angiography, and histology. Three of the allografts survived up to 105 days without any signs of rejection. High level of donor-specific chimerism for T-cell and B-cell lineages was maintained in the peripheral blood. The incisors continued to grow; teeth buds, bone, cartilage, and mucosa remained intact. Moderate inflammation of the nasal, oral mucosa, and keratinous metaplasia was noted histologically. We created a maxilla allotransplantation model that allows the study of immunologic responses and demonstrates potential clinical applications based on the growth properties of the allograft.

Is the lingual forming part of the incisor a structural entity?: Evidences from the fragilitas ossium ( fro/fro) mouse mutation and the TGFβ1 overexpressing transgenic strain

Our objective was to study the teeth of a mutant mice fro/fro that display severe forms of osteogenesis imperfecta. One day and 8 week-old fro/fro and +/fro heterozygote mice (wild type, WT) were processed for light and scanning electron microscopy. The genetic defect, shown to be located on chromosome 8, induced alveolar bone and teeth hypomineralisation. Due to defective cell proliferation in the fro/fro, the distal growth of the mandibular incisors was impaired. Immunolabelling revealed an increase of chondroitin/dermatan sulphate, whereas no difference was detected in dental tissues for decorin and biglycan. Amelogenin expression was decreased in the incisor and enhanced in the molar. Dentin sialoprotein was below the level of detection in the fro/fro, whereas osteonectin and osteopontin were unchanged. The main target of the mutation was seen in the lingual part of the incisor near the apex where dentine formation was delayed. In the molars, bulbous roots with obliteration of the pulp chamber were seen. In the TGFbeta1 overexpressing mice, the lingual root-analogue part of the incisor was missing. In the molar, short roots, circumpulpal dentine of the osteodentine type and pulp obliteration were seen. It may be noted that, although the mutant and transgenic strains mutations are two different genetic alterations not related to the same defective gene, in both cases the expression of the dentin sialoprotein is altered. Altogether, the present data suggest that the lingual forming part of the incisor seems to be an anatomical entity bearing its own biological specificities.

Autonomic neural signals in bone: Physiological implications for mandible and dental growth

Signals derived from the autonomic nervous system exert potent effects on osteoclast and osteoblast function. A ubiquitous sympathetic and sensory innervation of all periosteal surfaces exists and its disruption affects bone remodeling. Several neuropeptides, neurohormones and neurotransmitters and their receptors are detectable in bone. Bone mineral content decreased in sympathetically denervated mandibular bone. When a mechanical stress was superimposed on mandibular bone by cutting out the lower incisors, an increase in bone density ensued providing the sympathetic innervation was intact. A lower eruption rate of sympathetically denervated incisors at the impeded eruption side, and a higher eruption rate of denervated incisors at the unimpeded side were also observed. A normal sympathetic neural activity appears to be a pre-requisite for maintaining a minimal normal unimpeded incisor eruption and for keeping the unimpeded eruption to attain abnormally high velocities under conditions of stimulated incisor growth. These and other results suggest that the sympathetic nervous system plays an important role in mandibular bone metabolism.

Effect of ultrasound on rabbit mandibular incisor formation and eruption after mandibular osteodistraction

Therapeutic ultrasound is known to enhance bone-fracture healing. The purpose of this article was to study the effect of therapeutic ultrasound on mandibular incisor development and eruption in 15 skeletally mature male New Zealand white rabbits undergoing mandibular osteodistraction. The surgical cuts were made anterior to the molars and consequently transected the mandibular incisors. The animals were divided into 3 groups of 5 rabbits each. Group I received ultrasound on both sides of the mandible every other day. Group II received ultrasound on the left side of the mandible every day. Group III did not receive ultrasound. Ultrasound was given for 20 minutes per application. Mandibular incisor eruption was measured directly on the rabbits and on lateral head radiographs. The animals were killed 4 weeks after surgery, and dissected mandibular specimens that contained the incisor segments were evaluated histologically. The lengths of the tooth segments increased in the ultrasound-treated animals, compared with the controls (group III). However, the rabbits in group II had greater increases in length of the mandibular incisor segments than those in group I. Histologic examination showed that the newly formed tissues at the distraction site and at the cut ends of the incisor segments consisted of osteodentin-like tissue and cementum. Thus, therapeutic ultrasound combined with distraction enhanced mandibular incisor growth and eruption.

Epithelial-induced intrapulpal denticles in B6C3F1 mice.

Multiple intrapulpal denticles were observed in maxillary incisors of control and treated B6C3F1 mice used in a chronic inhalation study. Histologically, the denticles originated from multiple small budlike projections emanating from the epithelial sheath, immediately adjacent to the pulp chamber. The denticles were round to ovoid in shape with a central cavity surrounded by tubular dentin. Immature denticles contained epithelial cells within the central cavity, whereas mature denticles were either devoid of cells or contained cell fragments. A layer of columnar odontoblasts surrounded the outer surface of each denticle. Denticles advanced in a coronal direction as the incisors grew. With continued incisor growth, some denticles impacted the tooth wall and were associated with defects in dentinogenesis, altered tooth shape, and microfractures. Some denticles became partly or entirely incorporated into the dentin of the tooth. Intrapulpal denticle formation may represent a previously unidentified alteration that could contribute to the development of dental dysplasia in mice by interfering with normal tooth development and predisposing affected teeth to malformation and biomechanical failure with fracture.

Time-related changes of developing enamel crystals after exposure to the tissue fluid in vivo: analysis of a subcutaneously implanted rat incisor.

To investigate the effects of tissue fluid on the growth of enamel crystals, upper and lower incisors extracted from 3-week-old Wistar rats were removed of the enamel organ, implanted subcutaneously in the dorsal portion of animals from the same litter, and harvested at 72 h or 1 week after implantation. The grafts were chemically fixed with surrounding tissues and prepared for light and electron microscopy, X-ray microanalysis, or for the immunohistochemistry of amelogenin. Mineralization of implanted enamel layers was examined by contact X-ray microradiography. The immunoreactivities for 25 kD amelogenin in immature enamel decreased sequentially, starting from the surface to the deeper layers; by 1 week after implantation, no positive reactivities remained in the entire enamel layers at the stages of matrix formation and early maturation. In accordance with the loss of enamel proteins, immature enamel gained mineral density until it attained higher radio opacity than that of the adjacent dentin by 1 week. In contrast, the radio opacity of the full thickness of the enamel at early maturation remained low except for a superficial thin layer. Electron microscopy revealed no sign of growth of original enamel crystals, but showed heavy precipitation of electron-dense fine granules of calcium phosphate in all layers of the secretory enamel and the superficial layer of enamel at early maturation, which showed high radio opacity. The Ca/P ratio and electron diffraction patterns of the granular materials precipitated between intrinsic enamel crystals indicated the property of hydroxy apatite or octacalcium phosphate though a characteristic ribbon-like profile of enamel crystals was lacking. These data indicate that the enamel organ blocks exogenous mineral precipitates in growing enamel during the stage of matrix formation and plays an essential regulatory role for fine enamel crystallites to grow into large hexagonal crystals.

Incisor Adaptation to Fossorial Life in the Blind Mole-Rax Spalax ehrenbergi

Blind mole-rats (Spalax ehrenbergi) are aggressive and solitary fossorial rodents, highly specialized to their environment. They use their lower incisors mainly to excavate their tunnel systems. We found that the lower incisors of the mole-rat grow significantly faster than the upper incisors. Upper and lower incisors of males grow significantly faster than incisors of females. Density of incisors of males was significantly higher than in females and in male laboratory rats (Rattus norvegicus). In both sexes of mole-rats, maxillary bone density at the root apex area of the incisor was significantly higher than the anterior area where incisors emerge from the bone and the same area densities in male laboratory rats. We suggest that the rapid growth rate and high density of incisors in mole-rats compared with male laboratory rats represent an adaptation to their digging life-style and compensate for the extensive incisor attrition resulting from the mechanical forces of digging. Inter-sexual differences in mole-rat incisor growth and incisor plus maxillary bone densities are in accordance with intersexual behavioral differences: males excavate wider and longer tunnels than females and are more aggressive. Because incisors of males are used more extensively in digging and fighting than those of females, we suggest that male mole-rats develop stronger incisors with a higher compensatory growth rate than females.

Laminin and collagen IV distribution and ultrastructure of the basement membrane of the gingiva of the rat incisor.

The continuous growth of the rat incisor is associated with renovation of the junctional epithelium and resorption of the periodontal ligament. The circumdental papilla separates the connective tissue suffering resorption from the rest of the gingiva. Laminin and collagen IV were detected by the immunoperoxidase technique on the basement membrane of all regions of the gingival epithelium of the rat incisor, except the internal basal lamina and the internal surface of the circumdental papilla. The internal basal lamina is formed by a granular electron-dense material, without the organization of a typical basal lamina. Areas of the internal surface of the circumdental papilla, negative for laminin and collagen IV, lack the basal lamina. These data suggest that these molecules are not components of the dento-epithelial junction of the distal surface of the rat incisor. In addition, the basal lamina is absent or fragmented on the internal surface of the circumdental papilla, adjacent to the areas of the connective tissue undergoing resorption.

Long-term stability of Angle Class II, Division 1 malocclusions with successful occlusal results at end of active treatment

The purpose of this study was to examine long-term stability of Angle Class II, Division 1 malocclusions with successful occlusal results at the end of active appliance therapy, search for predictors of relapse, and look for characteristics associated with successful treatment. Records taken before and after treatment and a mean of 14.0 years postretention of adolescent patients treated for a significant Angle Class II, Division 1 malocclusion both with and without tooth extraction were evaluated. The sample was limited to successfully treated cases as judged by subjective evaluation of intercuspation and incisor occlusion of posttreatment study models and included 78 patients. Cephalometric characteristics or postretention occlusion was not considered in sample selection. The mode response was no change postretention for molar, premolar, and canine relationships and relapse of 0.5 mm for overjet and overbite. Maximum relapse was 3.5 mm for molar, premolar, and canine relationship, 3 mm for overjet, and 4.5 mm for overbite. Stepwise backward multiple regression analyses revealed no associations between either pretreatment characteristics or skeletal and dental treatment changes and relapse of overjet. However, relapse of overjet was associated with relapse of molar, premolar, and canine relationships, postretention increase in overbite, postretention proclination of maxillary incisors, and postretention retroclination of mandibular incisors. Active treatment changes included redirection or inhibition of maxillary growth and retraction of maxillary incisors. Mandibular incremental growth was favorable both during and after treatment. It was concluded that successful correction of Angle Class II, Division 1 malocclusions through differential growth adaptation and tooth movement appears to be very stable. (A M J O RTHOD D ENTOFAC O RTHOP 1995;107:276-85.)

Growth hormone and insulin-like growth factor-I in odontogenesis.

This review documents recent insights into the roles of growth hormone and insulin-like growth factor-I during tooth formation. Hereditarily growth hormone-deficient Lewis dwarf rats and hypophysectomized rats have been used to document the influence of growth hormone on growth of the rat incisor and molar teeth in vivo. Cell population studies using bromodeoxyuridine labeling have shown that growth hormone administration to dwarf rats affects odontogenic cell proliferation in the incisor teeth. Immunohistochemistry, employing well-characterized monoclonal antibodies directed against the hormone, its binding protein/receptor, the growth factor and its receptor, has enabled the location of these proteins to be mapped in the ontogenic sequences of ameloblasts, odontoblasts and cementoblasts. This mapping is consistent with the concept that differentiating odontogenic cells are targets for the hormone and that insulin-like growth factor I is implicated as a secondary messenger in the same differentiating cell populations. The content of predentine and precementum matrices proteoglycans appears to be growth hormone-dependent. The proteoglycans implicated so far are rich in chondroitin sulphate and thus they may also be insulin-like growth factor I (sulphation factor)-dependent. Thus matrix synthesis may be what is principally affected by growth hormone in odontogenesis although no evidence of an effect on enamel matrix synthesis or proteoglycan content has yet been documented.

A light and electron microscopic study on pulpal nerve fibers in the lower incisor of the mouse.

Light and electron microscopic studies were made on pulpal nerve fibers in mouse lower incisors, typical continuously growing teeth. Serial sections, from the apex of the odontogenic sheath to the incisal edge of the apical foramen, were examined by light microscopy to identify myelinated fibers passing through the apical foramen. The fine structure of the pulpal nerves was examined by electron microscopy at three sites: 1) the level at the incisal edge of the apical foramen; 2) a level 5 mm incisal from the apex of the odontogenic sheath; and 3) the level where the incisor comes out of the alveolar bone. No myelinated fibers were found passing through the apical foramen; they were also lacking at the three levels of the pulp. At level 2, unmyelinated axons were seen in close contact with smooth muscle fibers of arterioles. At level 3, nerve fibers were difficult to distinguish from processes of fibroblasts and odontoblasts. Degenerating axons were present in Schwann cells, and fine unmyelinated axons running through the odontoblast cell layer were seen. Various types of unmyelinated axons were observed in the apical region (level 1). These axons were classified into 6 types on the basis of their fine structures: Type I, bundles of unmyelinated axons completely or partly ensheathed by Schwann cell cytoplasm (mature type); Type II, bundles of unmyelinated axons in a space formed by a Schwann cell membrane (regenerating type); Type III, bundles of unmyelinated axons ensheathed not by a Schwann cell, but merely by a basal lamina (regenerating type); Type IV, single axons in direct contact with the basal lamina (regenerating or terminal type); Type V, naked, electron-dense axons with many vesicles and mitochondria (growth cone-like type); and Type VI, electron opaque axons, due to loss of axonal organellae (degenerating type). The significance of these structures is discussed in relation to the continuous growth of the rodent incisor.

Incisor growth in voles

Incisor growth was studied in three species of voles: Clethrionomys glareolus (Schreber, 1780) (C. g.), Microtus agrestis (Linnaeus, 1761) (A/. ag.) and Microtus arvalis (Pallas, 1779) (M. ar.). All animals were given tetracycline hydrochloride intramusculary or per os, and were anaesthetized or killed on the 9-14 day after treatment. Longitudinal and cross ground sections and cross sections stained with hematoxyline were investigated. Incisor growth was expressed by eruption rate, the time of complete incisor reneval and rate of dentin apposition. The rate incisor eruption was greater in maxilla than in mandible and higher in M. ar., and M. ag. than in C. g. It decreased with age in both studied voles ( M. ag., C. g.). The time of complete renewal of upper and lower incisors was similar. The rate of dentin apposition was different in upper and lower incisors, in different parts of the same tooth and in difTeren species of voles. In labial, lateral and lingual walls of upper incisors of the voles studied and in lower incisors of M. ar. an increase in the rate of dentin apposition was observed from the basal to the medial part of the tooth. In the medial wall of incisors a reverse tendency was seen in all voles. Daily layers of dentin were recognized in all incisors, but the greatest contrast was seen in M. ar. and the least visible, in C. g. Appositional layers in incisor dentin could be used for indirect determination of the rate of incisor eruption.

Evaluation of chemical protection against radiogenic osteodentin synthesis.

The effect of the radioprotector 2-mercaptopropionylglycine (MPG) in preventing the synthesis of radiation-induced osteodentin was examined. Fifty rats were exposed to single x-ray doses of between 3 and 19 Gy localized to the maxillary incisor growth centers. Half of the animals received an injection of MPG before irradiation while saline was administered to the other rats. MPG produced statistically significant reductions in the severity of osteodentin generation, but not its frequency, at some radiation levels. The nature of osteodentin and possible mechanisms of chemical radioprotection by MPG are discussed.

A computerized histomorphometric study of the effects of intoxication with vitamin D3 or 1,25 (OH)2D3 on growth and dentin production of impeded and unimpeded rat incisors

The effects of Vitamin D3 and 1,25(OH)2D3 intoxication on growth and dentinogenesis were studied in impeded and unimpeded rat incisors. Animals were intoxicated either with Vitamin D3 (2 mg/kg/day) or 1,25(OH)2D3 (400 ng/kg/day) for 19 days. Undecalcified transverse sections were obtained from all lower incisors. The outlines of all dental tissues were traced and fed into a computer which depicted the changes in all variables measured (circumference and cross-sectional area of tooth, pulp and dentin, width of dentin, CEJ [cemento-enamel junction] diameter and maximal labio-lingual diameter). Eruption rates, which had been recorded previously every 48 h, were used to compute the physiological age of each tooth site, so that only areas of similar age be compared. Growth. External dimensions of all intoxicated teeth decreased as the experiment progressed in contrast with control incisors which continued to increase in size. This effect was more pronounced in unimpeded incisors and may be due to the inhibitory influence of 1,25(OH)2D3 on cellular proliferation at the apical progenitor end. Dentinogenesis. 1,25(OH)2D3 intoxication had no significant effect on the rate of eruption and dentin formation in both impeded and unimpeded incisors. The same was true for impeded incisors intoxicated with Vitamin D3 but, both eruption and dentin production rates were impaired in Vitamin D3 unimpeded incisors.

Orally administered methionine alters the growth of tooth germs in newborn rats.

The effects of methionine intubation via gastric needle on the growth of incisor and molar tooth germs in newborn rats were investigated. Upon delivery, the pups were divided into groups of 8 and randomly assigned to dams which were then randomly assigned to three groups. Then the pups were intubated in the stomach with (a) no methionine - group I, (b) 0.1 g methionine per 100 g body weight - group II, or (c) 0.2 g methionine - group III, from day 3 to day 13 on every other day. At day 15, the average body weights of pups among the three groups showed no difference statistically, though animals in group III showed a 17.5% mortality rate; there were no deaths in the other two groups. There was inadequate hair growth in some pups in group III. The weights of incisor and of molar tooth germs in group II were heavier than in groups I and III. The total hydroxyproline content of incisor tooth germs in group II was also greater than in the other groups, whereas there was no difference in molar tooth germs on this parameter among all groups. Collagen synthesis of both tooth germs was highest in group III compared to other groups. The total amount of calcium in both tooth germs showed no difference among groups, but values were consistently higher in group II. 45Ca uptake showed no difference among groups. The present results indicate that the amount of methionine received by growing pups alters the composition of developing tooth germs, but that incisor and molar tooth germs are affected differently.

Age-related and 224Ra-induced abnormalities in the teeth of male mice

A high incidence of incisor abnormalities was found in aged control and aged 224Ra-treated male CBA mice. Visual examination of the abnormalities in both controls and treated mice revealed extreme shortening of the upper incisors and hypoplastic, grooved or undulating enamel. The administration of 865 or 1730 nCi of 224Ra hastened the onset of incisor abnormalities although no specific feature was attributable solely to radium toxicity. Radiography and histology revealed corrugated incisors, obliteration of the pulp cavity, extension and disorganized growth of incisors basally, secondary incisors, open pulp and fractures within the alveoli. There was a statistically-significant reduction in the number of molars present in animals given 432, 865 or 1730 nCi 224Ra.

Effects of prenatal malnutrition on development of oral tissue in neonatal rats.

The effects of prenatal malnutrition on the growth of incisor and molar tooth germs and tongue were investigated in newborn rats. Compared with the results on the young of well-nourished mothers, the young of the malnourished animals had fewer and smaller cells in the molar tooth germs and fewer cells in incisor tooth germs. The tongue of the malnourished animals had fewer but larger cells. 45Ca uptake studies and alkaline and acid phosphatase activities suggested that prenatal malnutrition affected incisor and molar tooth germs in different ways. Alkaline phosphatase activity in the tongue did not differ between dietary groups. The results indicate that an adequate protein intake is extremely important for the healthy development of the teeth and tongue of the offspring.

The coincidence between a distinct accessory groove in young dugong teeth and a tropical cyclone

Four queensland dugong skulls from animals which died on known dates in 1965, all having permanent incisor growth layer numbers of 2 or less, were used to establish the coincidence between a disturbance mark in the teeth and a tropical cyclone. Two had a distinct accessory groove in the last complete ridge to be deposited, and this was present but less distinct in the third. Since growth layers are now known to be annual, the deposition times of ridge and groove material during 1965 were estimated using additional material, and the possible time of formation of the accessory groove determined as January to March. The fourth animal showed no accessory groove. The growth disturbance causing the accessory groove must occurred before or about the time of its birth, estimated as the end of January 1965 at the earliest. Cyclone Judy occurred at that time and its relevance is discussed.

A Case of Abnormal Growth of Incisors of Albino Rat

A case with abnormally grown incisors was found among a group of male albino rats raised with powder feed. The amimal was 90 days old. It had a body weight of 116 grams and a body length of 150mm. Morphological and radiographical observations of the incisors were therefore made.1. The right upper incisor had recurved, penetrated through the bone of the palate into the right incisive foramen, and grown into the maxilla.2. The left upper incisor had followed the line of a complete circle.3. The measurement of this amimal incisors was as follows: The right and left upper teeth measured 26.7 and 29.3mm in length, and the lower teeth 21.0 and 17.3 mm. The right and left upper teeth were 1/6.75 and 1/5.64 in curvature (1/r), and the lower teeth 1/16.7 and 1/12.7.4. The cusps of the left upper and the right lower incisors were sharped edge, and the tip of the left lower incisor was chisel-sharped edge. In the soft-radiographic finding, the tip of the left upper incisor was chisel-sharped edge.5. These teeth were imparted a yellow-orange colouration to the enamel surface except tips imparted a milk-white.6. The lower incisors curved to the right side of the head made 6mm×6mm wound in the right cheek.7. The deviation of the jaws was about two degree.8. The both mandibular condyles and glenoid fossa were normal shape.Beretta (1913) made an analysis of abnormally grown incisors and classified them in three groups. It seems probable that this case was overgrowth due to deviation of the jaws.

In vitro collagen synthesis of tooth germs from newborn rats with protein-energy malnutrition.

Mineralization and matrix formation are closely related processes in the growth and development of both incisor and molar tooth germs. Addition of ascorbic acid does not affect in vitro collagen synthesis of tooth germs from protein-energy malnourished rats.