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Immunolocalization of heat shock protein 70 during reparative dentinogenesis.

OBJECTIVE: To investigate the immunolocalization of heat shock protein 70 (hsp 70) during reparative formation and to discuss the role of heat shock response in dental pulp injury and repair. METHODS: A single cavity was prepared in the mesial surface of the first molars of both maxilla and mandible in Wistar rat. The animals were sacrificed at 3, 15, and 30 days post-operation. After the histological process, the paraffin sections were reacted with monoclonal antibodies against rat hsp 70 using the strept-avidin-biotin-peroxidase complex method. RESULTS: Immunolocalization demonstrated heavy staining for hsp 70 in normal pulp and at different stages of dental pulp repair. In normal pulp, immunoreactivity was visualized in the odontoblasts and the pulp fibroblast. In the group sacrificed at 3 days, heavy staining was located in the odontoblast process and cytoplasm. After 15 days, the newly formed odontoblast-like cells were strongly stained. At 30 days, the same staining intensity was observed in odontoblast-like cells and in pulp cells. No staining was seen in reparative dentin. CONCLUSION: These results demonstrated that heat shock protein 70 might play an important role as a molecular chaperone during reparative dentin formation.

Animals↗

Extracellular fluid movement in the pulp; the pulp/dentin permeability barrier.

Fluid movement in the pulp depends largely upon the physiology of the blood vessels; normally there is a net efflux of fluid and proteins from the capillaries into the extracellular environment. Most pulp capillaries lie close to the odontoblast layer and in order to see whether fluid can pass between the odontoblasts into the predentin we have perfused the vessels of molar tooth germs in anesthetized piglets with the electron dense tracer lanthanum. The results show that the tracer permeates the capillaries but encounters a barrier to permeability at the apical (predentinal) ends of the odontoblasts. The completeness of the barrier to the tracer lanthanum is discussed together with structural evidence of tight junctions between odontoblasts in both pigs and humans and the presence of collagen fibers through the tight junctional zone. It is concluded that there is little or no evidence that pulp fluid is normally confluent with predentin. An advantage of this arrangement may be that by maintaining an enclosed microenvironment it permits regulation of the orderly process of matrix deposition and mineralization of predentin to dentin. In order to maintain constant vascular and extracellular fluid pressures the capillary efflux has to be balanced by fluid removal; recent work in cats has shown that lymphatic vessels are available to transport fluid out of the pulp. In this paper the differences in the intrapulpal distribution of these vessels have been extrapolated to human teeth in an attempt to explain certain variations in the symptoms and progress of pulpal inflammatory conditions.

Animals↗

[Neurocristopathic classification of dental abnormalities].

The neural crest of the vertebrae provides the odontoblasts, which by migrating in the stomodeal epithelium induce in the latter the formation of predamantoblasts (enamel cell). The odontoblasts are then the point of departure of tissue interactions (ectodermal and neurectodermal) which characterise dental organogenesis. An analytical neurocristopathic classification of this organogenesis based upon the developmental properties of the odontoblast is suggested: --abnormalities of formation (anodontism, hypodontism); --abnormalities of migration (ectopism); --abnormalities of cell differentiation and multiplication (hypodontism, microdontism and macrodontism, disturbances in odontogenesis and their combinations, disturbances in amelogenesis). "No odontoblast, no tooth". The dental organ is an indicator of the developmental biological activity of the neural crest as well as its neurulation. Abnormalities in dental organogenesis are of predictive value in terms of other abnormalities of cephalogenesis, those related to the differentiation of the other cells of the neural crest (bone, muscle, cartilage) and those related to the neural tube with which they are territorialised: these are dysneurulations. This classification covers the clinical features of dental abnormalities seen in pediatric stomatology.

Humans↗

On the incremental lines in human dentine as revealed by tetracycline labeling.

Growth of human dentine was investigated in extracted permanent teeth exhibiting more than two tetracycline lines. It was concluded that: (1) The secretory activity of an odontoblast varies considerably during its life cycle, and likewise the rate of migration of the odontoblast cell body varies. Odontoblast secretion and migration as a general rule start slowly, reach a peak and then slow up as dentine production nears completion. (3) The activity of a particular odontoblast varies with the type of tooth with which it is associated and with its position within the tooth, as well as with the particular stage reached in its life cycle.

Anthropometry↗

Effect of ascorbic acid deficiency on mouse second molar tooth germs cultivated in vitro.

Mandibular second molar tooth germs from two-day old mice were cultured in vitro, on millipore membranes, for periods of up to 20 days in liquid medium with or without added ascorbic acid. Tooth germs grown in ascorbate medium were characterized by relatively normal growth, differentiation, morphology and histology. Cuspation patterns were maintained. The epithelial root sheath continued to grow along the millipore membrane. Tooth germs cultured in ascorbate-deficient medium manifested a consistent and striking failure in maintenance of differentiated odontoblastic and ameloblastic tissue with arrest of predentin synthesis, severe structural collapse and reduction in size. Cuspation patterns were lost in scorbutic molars, with sinking of surface layers into pulpal tissue and flattening of the entire organ. This resulted in a lack of recognizable morphology and in severe disorganization of tissues. Only growing areas of the root sheath with associated proliferation of preameloblasts and pre-odontoblasts and adjacent pulpal tissue remained normal and refractory to ascorbate deficiency. Odontoblastic as well as ameloblastic layers were disrupted and cells were dedifferentiated. Newly differentiated odontoblasts became highly vacuolated when they became polarized and started to secrete extracellular matrix.

Ameloblasts↗

Mineralization patterns in elasmobranch fish.

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

Animals↗

Cell- and stage-specific expression of vitamin D receptor and calbindin genes in rat incisor: regulation by 1,25-dihydroxyvitamin D3.

To investigate the extent of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] action and its relationships to calbindin gene expression in mineralized tissues, we have analyzed rat incisors with different probes, including a vitamin D receptor (VDR) antibody and specific cDNAs to rat calbindin-D9K and calbindin-D28K. Developmental and hormonal controls of calbindin gene expression were investigated by Northern blot analysis of ameloblast and odontoblast mRNA. Distribution and hormone-induced changes of VDR were also studied by light microscopic immunocytochemistry. A differential tissue- and stage-specific expression of the calbindin genes was observed in microdissected portions of the continuously erupting incisor. The two calbindins were expressed in ameloblasts, whereas only calbindin-D28K was expressed in odontoblasts. Moreover, in ameloblasts, expression of calbindin-D28K preceded that of calbindin-D9K. Immunoreactivity for VDR was present in all progenitor cells and progressively decreased during the differentiation process, whereas, in differentiated tissues, a hormonal upregulation was restricted to hard tissue-forming cells, i.e., ameloblasts and odontoblasts. Furthermore, calbindin gene expression appeared to be regulated by 1,25(OH)2D3. Taken together, these data indicate that ameloblasts and odontoblasts are target cells for 1,25(OH)2D3 and provide the first insights into the hormonal control of tooth genes during development.

Animals↗

Immunohistochemical localization of connexin 43 in the developing tooth germ of rat.

Distribution of gap junction protein in maxillary tooth germs of 1-day-old rats was examined by immunohistochemistry, using an affinity-purified antibody specific to residues 360-376 of rat connexin (CX) 43. In 1-day-old rats, the maxillary second molar formed the shape of the cusp, but neither dentine nor enamel was formed between the cells of the dental papilla and the inner enamel epithelium. In the tooth germ, CX 43 was expressed in the cells of the stratum intermedium and the inner enamel epithelium. Labelling in the stratum intermedium was extensive and showed an increasing gradient from peripheral to cuspal regions. CX 43 detected in the inner enamel epithelium was at cell surfaces facing the interface between the dental papilla and the inner enamel epithelium. The cells of the dental papilla and the inner enamel epithelium began differentiation as odontoblasts and secretory ameloblasts respectively, in the cusps of the first molars, where predentine and dentine were formed but enamel matrix was not secreted. CX 43 was present in the stratum intermedium, inner enamel epithelium, preodontoblasts, odontoblasts and subodontoblasts. The incisors showed the most advanced stage of development, where the enamel matrix and calcified dentine were formed in the labial part of the teeth. The CX 43 epitope was seen in the stratum intermedium, inner enamel epithelium, preameloblasts, preodontoblasts, odontoblasts, and subodontoblasts. Immunolabelling was more extensive in the stratum intermedium and subodontoblasts than in preameloblasts, preodontoblasts, and odontoblasts. The immunolabelling in preameloblasts and predontoblasts was accumulated at cell surfaces facing the predentine.(ABSTRACT TRUNCATED AT 250 WORDS)

Ameloblasts↗

Cyclophosphamide-induced changes in rodent odontogenesis. A light- and electron-microscopic study.

Cyclophosphamide-induced changes in rodent odontogenesis were investigated by light and electron microscopy in four-day-old Sprague Dawley rats given one injection of 40 mg/kg of body weight of cyclophosphamide and killed at intervals of one hour, one day, one week and two weeks. Incisor and molar teeth were dissected from the animals, fixed in 2.0% glutaraldehyde in 0.1 M sodium cacodylate with 3.4% sucrose, and subsequently some were incubated for alkaline phosphatase reaction, and embedded in Spurr's medium for sectioning at light- and electron-microscopic levels. From three days a cell-sparse zone was created in the pulp in the growing end of the tooth and progressive cellular changes were observed which became more severe in the one-week and two-week specimens. Subodontoblast and adjacent pulpal cells were the most affected showing nuclear changes, damage to, or loss of, organelles, and inclusion bodies. Odontogenic epithelium was less affected and odontoblasts appeared to be unaffected by the drug. A new irregular matrix was laid down in the defect area and seemed to be the product of depolarized odontoblasts. This new matrix showed alkaline phosphatase activity, as did the cells embedded in it, and later it became mineralized. It is speculated that the polarity of odontoblasts might be maintained by an intact subodontoblastic layer; when this is lost the odontoblasts become depolarized and capable of secreting matrix from both ends.

Aging↗

The structure and development of the collar enameloid in two teleost fishes, Halichoeres poecilopterus and Pagrus major.

Histologically the outer layer of the collar enameloid obviously differs from the inner layer, and it has a degree of mineralization nearly as high as the cap enameloid which has the highest. In the stage of matrix formation, the organic matrix of the collar enameloid contains a number of collagen fibers, and odontoblasts display features suggesting that these cells actively synthesized and secreted collagen. A number of cell processes, matrix vesicles and some cell debris which were probably derived from the odontoblasts were observed in the organic matrix of the collar enameloid. We consider that the majority of the organic matrix in collar enameloid originates from the odontoblasts. In the stage of maturation, collagen fibers were not observed in the outer layer of the collar enameloid in demineralized specimens. In the IDE cells during this stage, the complex infoldings of cell membranes developed in the distal portion, and several lysosomal granules and irregular-shaped granules containing many tubular structures, were observed in the distal cytoplasm. In the ODE cells, abundant labyrinthine canals appeared in the cytoplasm, and capillary vessels were found close to the outer surface of the ODE cells. We assume that the higher mineralized outer layer of the collar enameloid is made possible by the absorptive and transport functions of the epithelial cells during the stage of maturation. It is considered that the collar enameloid in this study was initially produced by the odontoblasts and then reconstructed by the epithelial cells, so that the collar enameloid differs from true enamel.

Animals↗

Expression patterns of Raf-1 suggest multiple roles in tooth development.

Raf-1, the product of proto-oncogene c-raf-1, has key roles in the signal transduction pathways within the cell. The molecular mechanisms of tooth development in the mouse embryo are not known in detail. We examined the expression of Raf-1 during subsequent tooth development by immunohistochemical analysis. In mouse embryos at days 12.5 post-coitum (p.c.), Raf-1 was expressed in the dental invaginating epithelium. At p.c. 13.5 (bud stage), Raf-1 was also expressed in the epithelial cells of the enamel organ, but not in the mesenchyme of the dental papilla. We added anti-proliferating cell nuclear antigen (PCNA) antibody as a marker for proliferating cells at early stages of tooth development. At p.c. 12.5 and p.c. 13.5, the staining patterns were very similar to that for Raf-1. At p.c. 15.5 (cap stage), Raf-1 could not be detected. At p.c. 17.5 (bell stage), Raf-1 was expressed in both the odontoblastic and subodontoblastic cells of the dental papilla. However, Raf-1 was not found in the epithelial cells of the enamel organ. We also added anti-type I collagen antibody as a marker for odontoblasts differentiation. The staining pattern for type I collagen antibody as a marker for odontoblasts differentiation. The staining pattern for type I collagen in odontoblasts was almost the same as for Raf-1. The results suggest that Raf-1 may play some roles in both cell proliferation and differentiation at different stages of tooth germ development.

Animals↗

An immunocytochemical study of pulpal responses to cavity preparation by laser ablation in rat molars by using antibodies to heat shock protein (Hsp) 25 and class II MHC antigen.

Initial responses of odontoblasts and immunocompetent cells to cavity preparation by laser ablation were investigated in rat molars. In untreated control teeth, intense heat shock protein (Hsp) 25 immunoreactivity was found in the cell bodies of odontoblasts, whereas cells immunopositive for the class II major histocompatibility complex (MHC) antigen were predominantly located beneath the odontoblast layer in the dental pulp. Cavity preparation caused the destruction of the odontoblast layer and the shift of most class-II-MHC-positive cells from the pulp-dentin border toward the pulp core at the affected site. Twelve hours after cavity preparation, numerous class-II-MHC-positive cells appeared along the pulp-dentin border and extended their processes deep into the exposed dentinal tubules, but subsequently disappeared from the pulp-dentin border together with Hsp-25-immunopositive cells by 24 h after the operation. By 3-5 days postoperation, distinct abscess formation consisting of polymorphonuclear leukocytes was found in the dental pulp. The penetration of masses of oral bacteria was recognizable in the dentinal tubules beneath the prepared cavity. These findings indicate that cavity preparation by laser ablation induces remarkable inflammation by continuous bacterial infections via dentinal tubules in this experimental model, thereby delaying pulpal regeneration.

Animals↗

Gene expression and immunolocalisation of amelogenins in developing embryonic and neonatal hamster teeth.

Amelogenins are a group of related matrix proteins, synthesised and secreted by ameloblasts during the formation of dental enamel. We have examined expression patterns and the tissue distribution of amelogenins by in situ hybridisation and by immunohistochemistry of developing teeth of embryonic (E12-E15) and neonatal (1- to 4-day-old) golden hamsters. Amelogenin expression and (intracellular) immunostaining for amelogenins were first observed in late embryonic stages in E14 incisors and E15 first molars in partially polarised pre-ameloblasts located along a thin layer of predentine before any overt deposition of enamel. Expression of mRNA and protein staining for amelogenins increased with age and early pre-dentine became immunopositive. The highest mRNA levels and substantial immunostaining for amelogenins were noted in neonatal-stage secretory ameloblasts fully engaged in enamel matrix deposition. After completion of the secretory phase, amelogenin gene expression continued at a lower level in post-secretory stages and was seen in transition-phase and maturation-phase ameloblasts. No amelogenin transcripts were observed in odontoblasts at any stage of their development. However, young odontoblasts stained weakly with anti-amelogenin antibodies before they formed the first layer of dentine, although this staining disappeared in odontoblasts at later stages of development. We conclude that amelogenin gene transcription occurs as early as the polarisation stage of pre-ameloblasts and is closely followed by translation of mRNA into amelogenin proteins. Odontoblasts do not transcribe the amelogenin gene and probably endocytose and digest amelogenins from the pre-dentine. Amelogenins are also transcribed but at a low level in post-secretory stages of amelogenesis.

Aging↗

The distribution and ultrastructure of class II MHC-positive cells in human dental pulp.

The distribution and ultrastructure of class II major histocompatibility complex (MHC)-positive cells were investigated in human dental pulp, employing immunohistochemistry using an anti-human leukocyte antigen (HLA)-DR-monoclonal antibody. HLA-DR-immunopositive cells, appearing spindle-like or dendritic in profile, were densely distributed throughout the dental pulp. Under the electron microscope, these cells exhibited various sizes of vesicles containing clear or opaque contents, multivesicular bodies and characteristic fine tubulovesicular structures in their cytoplasm. Some reactive cells possessed coated pits and vesicles including electron-dense materials, indicating an active endocytosis. At the periphery of the pulp tissue, the HLA-DR-immunopositive cells were predominantly situated in the subodontoblastic layer, with some located in the odontoblast layer and/or predentin and extending their cytoplasmic processes into the dentinal tubules. Cell processes of these cells occasionally made contact with several odontoblast processes in the same way as the nerve fibers in the predentin. These cells never contained the typical phagosomes frequently observed in the HLA-DR-immunoreactive macrophages in the subodontoblastic layer and the pulp core. The results suggest that the HLA-DR-immunopositive cells in the odontoblast layer and/or predentin have some regulatory function on the odontoblasts under physiological conditions, in addition to their involvement in the initial defense reaction after tooth injury.

Cytoplasmic Granules↗

The effect of epidermal growth factor on neonatal incisor differentiation in the mouse.

The effect of epidermal growth factor (EGF) on cellular differentiation of the neonatal mouse mandibular incisor was examined autoradiographically using tritiated thymidine ([3H]TDR) and tritiated proline ([3H]PRO). On days 0 (day of birth), 1, and 2, EGF was administered (3 micrograms/g body wt) sc to neonates. Mice were killed on Days 1, 4, 7, 10, and 13 after birth and were injected with either [3H]TDR or [3H]PRO 1 hr before death. [3H]TDR was used to analyze cell proliferation in eight cell types in the developing mouse incisor including upper (lingual) and lower (buccal) pulpal fibroblasts, preodontoblasts, inner and outer enamel epithelial cells (IEE and OEE), stratum intermedium (SI), stellate reticulum (SR), and periodontal ligament (PDL) fibroblasts. [3H]PRO was used to analyze protein synthesis in ameloblasts, and their secretion products (enamel and dentin), as well as PDL fibroblasts. The selected EGF injection scheme elicited acceleration of incisor eruption with minimal growth retardation. At Day 1, the upper and lower pulp, preodontoblasts, SI, and SR showed a significant decrease in labeling index (LI) 24 hr after a single EGF injection. After multiple injections (Days 0, 1, 2), two LI patterns were observed. In lower pulp, preodontoblasts, IEE, SI, SR, and OEE, a posteruptive change in LI was observed. In contrast, the upper pulp and PDL regions demonstrated a direct temporal relationship with eruption. Autoradiographic analysis with [3H]PRO indicated that EGF treatment caused significant increases in grain counts per unit area in ameloblast, odontoblast, and PDL regions studied. Significant differences were found in all four regions studied (ameloblasts, enamel, odontoblasts, dentin) at the 45-microns-tall ameloblast level as well as ameloblasts and odontoblasts at the 30-microns level at 13 days of age. The PDL demonstrated significant differences at all locations studied (base, 30 microns, 45 microns,) in 4-, 7-, and 13-day-old mice. Morphologically, EGF-treated groups demonstrated premature differentiation of ameloblasts and odontoblasts at the light microscopic level. The data indicate that EGF alters DNA and protein synthesis as well as differentiation patterns during the eruption process. While EGF affects both DNA and protein synthesis, the alteration of differentiation may be secondary to mitogenic effects on proliferative compartments. In order to determine the cellular target for EGF within the newborn mouse incisor, in vivo 125I-EGF binding was analyzed autoradiographically.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

mRNA expression and protein localization of dentin matrix protein 1 during dental root formation.

Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein. DMP1 was initially detected in dentin and later in other mineralized tissues including cementum and bone, but the DMP1 expression pattern in tooth is still controversial. To determine the precise localization of DMP1 messenger RNA (mRNA) and the protein in the tooth, we performed in situ hybridization and immunohistochemical analyses using rat molars and incisors during various stages of root formation. During root dentin formation of molars, DMP1 mRNA was detected in root odontoblasts in parallel with mineralization of the dentin. However, the level of DMP1 mRNA expression in root odontoblasts decreased near the coronal part and was absent in coronal odontoblasts. DMP1 protein was localized along dentinal tubules and their branches in mineralized root dentin, and the distribution of DMP1 shifted from the end of dentinal tubules to the base of the tubules as dentin formation progressed. During the formation of the acellular cementum, DMP1 mRNA was detected in cementoblasts lining the acellular cementum where its protein was localized. During the formation of the cellular cementum, DMP1 mRNA was detected in cementocytes embedded in the cellular cementum but not in cementoblasts, and its protein was localized in the pericellular cementum of cementocytes including their processes. During dentin formation of incisors, DMP1 mRNA was detected in odontoblasts on the cementum-related dentin, where its protein was localized along dentinal tubules near the mineralization front. The localization of DMP1 mRNA and protein in dentin and cementum was related to their mineralization, suggesting that one of the functions of DMP1 may be involved in the mineralization of dentin and cementum during root formation.

Animals↗

E- and N-cadherin distribution in developing and functional human teeth under normal and pathological conditions.

Cadherins are calcium-dependent cell adhesion molecules involved in the regulation of various biological processes such as cell recognition, intercellular communication, cell fate, cell polarity, boundary formation, and morphogenesis. Although previous studies have shown E-cadherin expression during rodent or human odontogenesis, there is no equivalent study available on N-cadherin expression in dental tissues. Here we examined and compared the expression patterns of E- and N-cadherins in both embryonic and adult (healthy, injured, carious) human teeth. Both proteins were expressed in the developing teeth during the cap and bell stages. E-cadherin expression in dental epithelium followed an apical-coronal gradient that was opposite to that observed for N-cadherin. E-cadherin was distributed in proliferating cells of the inner and outer enamel epithelia but not in differentiated cells such as ameloblasts, whereas N-cadherin expression was up-regulated in differentiated epithelial cells. By contrast to E-cadherin, N-cadherin was also expressed in mesenchymal cells that differentiate into odontoblasts and produce the hard tissue matrix of dentin. Although N-cadherin was not detected in permanent intact teeth, it was re-expressed during dentin repair processes in odontoblasts surrounding carious or traumatic sites. Similarly, N-cadherin re-expression was seen in vitro, in cultured primary pulp cells that differentiate into odontoblast-like cells. Taken together these results suggest that E- and N-cadherins may play a role during human tooth development and, moreover, indicate that N-cadherin is important for odontoblast function in normal development and under pathological conditions.

Adolescent↗

Nestin expression in embryonic and adult human teeth under normal and pathological conditions.

Nestin is an intermediate filament most related to neurofilaments and expressed predominantly in the developing nervous system and muscles. In the present study we examined the in vivo distribution of nestin in human teeth during embryonic development and in permanent teeth under normal and pathological conditions. The results show that nestin is first expressed at the bell stage and that its distribution is restricted in pulpal cells located at the cusp area of the fetal teeth. In young permanent teeth, nestin is found only in functional odontoblasts, which produce the hard tissue matrix of dentin. Expression is progressively down-regulated and nestin is absent from older permanent teeth. In carious and injured teeth, nestin expression is up-regulated in a selective manner in odontoblasts surrounding the injury site, showing a link between tissue repair competence and nestin up-regulation under pathological conditions. In an in vitro assay system of human dental pulp explants, nestin is up-regulated after local application of bone morphogenic protein-4. A similar effect is seen in cultures of primary pulp cells during their differentiation into odontoblasts. Taken together, these results suggest that nestin plays a potential role in odontoblast differentiation during normal and pathological conditions and that bone morphogenic protein-4 is involved in nestin up-regulation.

Adolescent↗