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Biomedical subjects

I Thesleff

Publications and source records attributed to I Thesleff.

172 records · Page 10Linked to original sources

Inhibition of tooth germ differentiation in vitro by diazo-oxo-norleucine (DON).

Molar tooth germs from mouse embryos were studied in a Trowell-type organ culture. After 5 days of culture the odontoblasts had secreted predentine and the ameloblasts had differentiated. When cultured in the presence of 10-50 micro M diazo-oxo-norleucine (DON), which is a glutamine analogue, the differentiation of odontoblasts was inhibited, but the teeth looked otherwise healthy. When DON was added after 2 days of culture in control medium (at this time the odontoblasts in the cuspal area were already differentiated), it did not inhibit predentine secretion, ameloblast differentiation, nor enamel secretion. However, this was seen only in the cuspal area and the boundary to the undifferentiated, more cervical cells was distinct. The results support the concept that the mechanism of the differentiation of odontoblasts is different from that of the ameloblasts. We have shown earlier that a close association between the basement membrane and the mesenchymal cells is required for odontoblast differentiation. Because DON interferes with glycosaminoglycan and glycoprotein synthesis we suggest that DON inhibits odontoblast differentiation by affecting the mesenchymal cell surface and/or the basement membrane.

Ameloblasts↗

Basement membrane formation in transfilter tooth culture and its relation to odontoblast differentiation.

The mesenchymal cells of the developing tooth differentiate into odontoblasts as a result of an epithelio-mesenchymal interaction. Odontoblast differentiation was studied in vitro by cultivating dental mesenchyme and epithelium with interposed filters. Separation of the two components by enzyme treatment resulted in removal of the basement membrane. When the epithelium was grown alone, or transfilter from killed lens capsule, the basement membrane was not restored. Transfilter cultivation with dental mesenchyme resulted in basement membrane formation, but only if the filter pores allowed penetration of cytoplasmic processes. Hence, a close association between the epithelial and the mesenchymal cells seems to be a prerequisite for the restoration of the basement membrane. Differentiation of odontoblasts took place only in explants in which a basement membrane was formed. Differentiation did not occur when contact of the mesenchymal cells with the basement membrane was prevented by small pore size filters. Further experiments demonstrating an intact basement membrane suggested that membrane contacts between the epithelial and the mesenchymal cells are not needed for odontoblast differentiation. Hence, we suggest that differentiation of odontoblasts is triggered via contact of the mesenchymal cells with the basement membrane.

Animals↗

Differentiation of odontogenic tissues in organ culture.

Molar tooth germs from 17-d-old mouse embryos were cultivated in a Trowell-type culture, and different culture media were tested for their ability to support enamel formation. The medium which allowed secretion of considerable amounts of enamel matrix by ameloblasts consisted of BGJb medium supplemented with 20% horse serum, 10% chick embryo extract and 0.9 mM ascorbic acid. At the onset of culture the teeth were in the early bell stage. After 2 weeks of cultivation both odontoblasts and ameloblasts had differentiated, and considerable amounts of predentin and enamel matrix had been secreted. Similar development was also seen in teeth which had been enzymatically separated into the mesenchymal dental papilla and epithelial enamal organ and subsequently recombined in vitro. This method allows good differentiation of odontogenic tissues, and is considered suitable for further studies of tissue interactions in the tooth rudiment.

Animals↗

Organ culture studies on human skin and cholesteatoma epithelium. Contact with connective tissue and exposure to vitamin A.

In tissue culture trunk skin from 8-day-old chick embryos showed a consistent change from keratinizing into more columnar non-keratinizing epithelium under the influence of vitamin A acid using concentrations from 10 to 20 IU/ml. Human adult postauricular and ear canal skin, cholesteatoma membrane, and human embryonic skin retained their keratinizing properties when exposed to vitamin A acid at concentrations up to 150 IU/ml, when toxic changes in the epithelium became obvious. Treatment of cholesteatoma ears with vitamin A ear drops is unlikely to effect any change in the keratinizing properties of the epithelium.

Animals↗

Epithelial-mesenchymal interactions in tooth morphogenesis: the roles of extracellular matrix, growth factors, and cell surface receptors.

Morphogenesis and cell differentiation in the developing tooth are controlled by a series of reciprocal interactions between the epithelial and mesenchymal tissues. The exact molecular mechanisms operating in these interactions are unknown at present, but both structural components of the extracellular matrix (ECM) and diffusible growth factors have been suggested to be involved. In this review article we summarize our findings on the distribution patterns of three ECM molecules and two cell surface receptors during tooth morphogenesis through bud, cap, and bell stages of development. The examined molecules include fibronectin, type III collagen, and tenascin, which all represent components of the mesenchymal ECM, the cell surface proteoglycan, syndecan, which functions as a receptor for interstitial matrix, and the cell surface receptor for epidermal growth factor. Based on the observed changes in distribution patterns and on experimental evidence, roles are suggested for these molecules in epithelial-mesenchymal interactions during tooth development. Fibronectin is suggested to be involved in the cell-matrix interaction that controls odontoblast differentiation. Epidermal growth factor and its receptors are suggested to be involved in a paracrine fashion in the epithelial-mesenchymal interactions regulating morphogenesis of bud- and cap-stage teeth. Tenascin and syndecan are accumulated in the dental mesenchyme during the bud stage of development, and it is suggested that they represent a couple of a cell surface receptor and its matrix ligand and that they are involved in mesenchymal cell condensation during the earliest stages of tooth morphogenesis.

Animals↗

[Interactions between the extracellular matrix and the cell surface determine tooth morphogenesis and the cellular differentiation of the dental mesenchyme].

A series of reciprocal interactions between epithelial and mesenchymal tissues control the morphogenesis and cell differentiation in the developing tooth. The molecular mechanisms operating in these interactions are, however, unknown at present. Structural components of the extracellular matrix (ECM) affect cellular behavior in the embryo and appear to be involved also in these regulatory processes. The ECM molecules exert their effects on cells through binding to specific matrix receptors on the cell surface. This review article summarizes our findings on the distribution patterns during tooth development of the ECM glycoproteins, fibronectin and tenascin, and of the cell surface proteoglycan, syndecan, which functions as a receptor for interstitial matrix. Based on the observed changes in these distribution patterns and on experimental evidence, roles for these molecules in epithelial-mesenchymal interactions during tooth development are suggested. Fibronectin and tenascin are enriched in the dental basement membrane at the time of odontoblast differentiation. These matrix glycoproteins may be involved in the cell-matrix interaction which controls differentiation of the dental mesenchymal cells into odontoblasts. Tenascin and syndecan are accumulated in the dental mesenchyme during bud stage of development. We have shown in tissue recombination experiments that the presumptive dental epithelium induces the expression of tenascin and syndecan in mesenchyme. We suggest that these molecules are involved in cell-matrix interactions, which regulate mesenchymal cell condensation during the earliest stages of tooth morphogenesis.

Basement Membrane↗

Does epidermal growth factor control tooth eruption?

Despite active research for more than several decades the factors responsible for tooth eruption have remained obscure. For a tooth to emerge in the oral cavity, to reach occlusion, and to continue eruption in adulthood, many changes in the tooth and its surrounding tissues occur; these changes must be synchronized. Epidermal growth factor appears to be involved in the eruptive process.

Animals↗

Histological observations of teeth and peridental tissues in cleidocranial dysplasia imply increased activity of odontogenic epithelium and abnormal bone remodeling.

Cleidocranial dysplasia (CCD) is a heritable generalized bone dysplasia presenting with a variety of dental abnormalities. To delineate morphological features of the dental tissues, we have analyzed histologically the structure of teeth and peridental tissues obtained from four CCD patients. Dentin appeared regular, except when formed in response to caries, physiological attrition or root resorption. Both acellular and cellular cementum were present in deciduous teeth, whereas in permanent teeth, cellular cementum was virtually lacking and acellular cementum was partially hyperplastic. Enamel pearls were seen in the furcations of one deciduous and one permanent molar. The roots of most deciduous teeth were resorbed only to a slight extent. Morphologically, supernumerary teeth resembled their normal counterparts. Denticles as well as epithelial cell clusters were occasionally present in the root pulps of deciduous teeth. In the peridental tissues, epithelium was locally abundant, and the cytokeratin profile confirmed its odontogenic origin. While the organization pattern of the alveolar bone matrix related to unshed deciduous teeth and unerupted permanent teeth varied, woven bone was abundant. Both formative and resorption surfaces were seen. Also, reversal lines were prominent, suggesting that the bone had, in fact, undergone remodeling. While no direct association between the aberrant bone morphology and the multifarious histological abnormalities of dental tissues can be established, the local abundance of odontogenic epithelium in peridental tissues of developing/unerupted as well as fully developed teeth may be causally related to the formation of excess acellular cementum, enamel pearls and supernumerary teeth.

Adolescent↗