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Biomedical subjects

I Thesleff

Publications and source records attributed to I Thesleff.

At least 163 records · Page 9Linked to original sources
PubMed1983

Exogenous fibronectin is not required for organogenesis in vitro.

The biological effect of plasma fibronectin on the differentiation of embryonic mouse kidney and tooth was studied in organ cultures. Transferrin (50 micrograms/ml) was a strong mitogen for kidney cells, whereas the addition of soluble fibronectin (50 to 250 micrograms/ml) had no detectable effect on differentiation or proliferation. The same serum-free, transferrin-containing medium did not support tooth differentiation. However, fibronectin was not a necessary serum component because fibronectin-free serum supported tooth development. It was demonstrated with antibodies specific for human fibronectin that the exogenously added human fibronectin at 50 micrograms/ml did not become incorporated to the cultured organs. Only minimal incorporation to the kidney basement membrane area was observed when fibronectin concentration was 250 micrograms/ml. The mesenchymal stroma and the basement membranes of the kidney and tooth rudiments cultured in fibronectin-free media stained intensely with conventional fibronectin antibodies, indicating endogenous production of fibronectin. Outgrowing epithelial cells from isolated kidney tubules produced fibronectin as well as laminin. The results suggest that the fibronectin found in the stroma and basement membranes is an endogenous product of the developing tissues and that plasma fibronectin is not required for in vitro organogenesis. The results also indicate that it is difficult to study the effect of fibronectin on morphogenetic processes because it may not penetrate the organ explants in vitro.

Animals↗
PubMed1983

Transferrin as a fetal growth factor: acquisition of responsiveness related to embryonic induction.

Differentiation of the metanephric mesenchyme, which is triggered by an inductive tissue interaction, has been shown to proceed in a chemically defined medium containing transferrin. Here, we report that neither transferrin-depleted serum nor a chemically defined medium devoid of transferrin promote differentiation and that activity can be restored by the addition of transferrin. It thus appears that we have identified the serum factor required for kidney differentiation. Transferrin seems to affect differentiation by stimulating cell proliferation. We show by using an organ-culture model system that only mesenchymes induced to differentiate by the 24-hr tissue interaction respond to transferrin by proliferation and differentiation, whereas uninduced mesenchymes remain unresponsive. The inductor tissue used is not responsive to transferrin. Thus, the data suggest that the short-range cell-mediated tissue interaction acts by making the nephrogenic mesenchyme responsive to the long-range mediator, which is transferrin. Transferrin is suggested to be an important circulating growth factor required for proliferation during embryogenesis.

Animals↗
PubMed1983

Inhibition of morphogenesis and stimulation of vascular proliferation in embryonic tooth cultures by a sarcoma growth factor preparation.

Sarcoma growth factor (SGF) induces proliferation and anchorage-independent growth of nonmalignant cells. It competes with epidermal growth factor (EGF) for the EGF-receptors at the cell surface. SGF-like factors have recently been isolated from embryos, suggesting that SGFs may represent embryonic forms of EGF. Therefore, we have tested whether SGF preparations affect organogenesis and differentiation of cultured embryonic tissues. The embryonic tooth rudiments were cultivated in the presence of SGF and EGF. Stimulation of vascularization was seen in both of these organ cultures. Therefore, we propose that endothelial cells may be target cells for SGF, and SGF may be involved in the control of vascularization during embryogenesis. SGF and also, to a certain extent, EGF profoundly inhibited morphogenesis and differentiation of the tooth germ, with concomitant stimulation of vascularization. Analysis of cell proliferation revealed that some cell types of the tooth germ did not respond to SGF by proliferation, while a stimulation by EGF was observed. Nevertheless, tooth morphogenesis was also slightly inhibited by EGF, suggesting that growth factors which enhance proliferation do not necessarily stimulate morphogenesis and differentiation. Since the SGF preparations contain several factors, the effects observed could be due to the action of one or more factors.

Animals↗
PubMed1982

Diazo-oxo-norleucine (DON)-induced alterations in the extracellular matrix of the mouse tooth germ.

In a previous study we have shown that the glutamine analogue diazo-oxo-norleucine (DON) inhibits the differentiation of mesenchymal cells into odontoblasts in the developing tooth. In the present study we have studied the effect of DON on the formation of the extracellular matrix by using light microscopic autoradiography and transmission electron microscopy. The inhibition of odontoblast differentiation was accompanied by alterations in the extracellular matrix at the epithelio-mesenchymal interface. The interface was reduced in space and filled with filamentous material, and the organization of collagen fibers in more advanced tooth germs was disturbed. DON also reduced the incorporation of [35S]sulphate into the basement membrane region, whereas no marked change was observed in the incorporation of [3H]fucose. These results suggest that DON affected the cell--matrix interaction which is believed to control the differentiation of odontoblast.

Animals↗
PubMed1981

Organogenesis in a defined medium supplemented with transferrin.

Organ culture of embryonic tissues provides means to analyse complex morphogenetic processes. Differentiation of the metanephrogenic mesenchyme into the epithelium of the nephron is know to occur in vitro. We have now formulated a synthetic medium which permits induction of the nephrogenic mesenchyme and its differentiation into the main segments of the nephron, the proximal and the distal tubules and primitive glomeruli. The medium consists of a basal medium supplemented with a single factor, transferrin. In the absence of transferrin differentiation failed to occur. None of the other factors tested (EGF, FGF, insulin, Pedersen fetuin) could replace transferrin.

Animals↗
PubMed1981

Ultrastructure of the epithelial-mesenchymal interface in the mouse tooth germ.

The structure of the epithelial-mesenchymal interface of a developing mouse embryonic tooth germ was examined at the time of cell differentiation by using transmission and scanning electron microscopy. During odontoblast differentiation, the basal lamina was continuous beneath the inner enamel epithelium, and the fibrils at the mesenchymal aspect increased in density and length. Numerous cell processes of the preodontoblasts were seen in close contact with the basal lamina. This supports the idea that the basement membrane is involved in the differentiation of mesenchymal cells into odontoblasts, probably by providing special attachment sites for the aligning mesenchymal cells. The rearrangement of intracellular organelles in the cells of enamel epithelium and a change of epithelial morphology were already seen at the time of the initial predentin secretion by odontoblasts. At this time, the basal lamina was still present. The penetration of epithelial microvilli into the epithelial-mesenchymal interface through breaks in the basal lamina related to the onset of predentin mineralization. This suggests that the determination of epithelial cells into ameloblasts already occurs before the disappearance of the basal lamina.

Ameloblasts↗
PubMed1980

Tunicamycin inhibits mouse tooth morphogenesis and odontoblast differentiation in vitro.

Tunicamycin (TM), an antibiotic that selectively inhibits dolichol-mediated protein glycosylation, inhibited morphogenesis and differentiation of odontoblasts in the molar tooth germ in vitro. These effects of TM are reversible and dose-dependent, and in advanced teeth the effect of TM was not complete unless the basement membrane was removed prior to culture. TM did not prevent secretion of predentin or enamel when added to the cultures after initiation of predentin secretion. TM dramatically inhibited protein glycosylation and the accumulation of labeled proteoglycans and glycoproteins in the basement membrane. Our previous studies indicated that odontoblast differentiation is triggered by an interaction between the basement membrane and mesenchymal cells. We suggest that TM inhibits odontoblast differentiation by causing alterations in the basement membrane which prevent the necessary cell-matrix interaction required for odontoblast differentiation.

Animals↗
PubMed1979

Effect of caries in mentally handicapped children of addition of fluoride and bicarbonate-phosphate to dietary sugar products.

Mentally handicapped children, aged 5--15 years and living in institutions, received fluoride supplement in several sugar products of their diet; in candies, marmalades, jams, fruit juices and in sweet desserts corresponding to 10 mg F as NaF per kg of the sugar (sucrose or glucose) of each product. To two of the four daily candies was also added a NaHCO3 + KH2PO4 mixture (mole ratio 9.8/l, resp.) to substitute for 2.5% of the sugar of the candy. The control children received the respective products without the additives. After stepwise exclusions of subjects for various reasons, e.g. for the absence of permanent teeth, low initial caries activity, strong medication, Down's syndrome, etc., the mean DMFS-increment in the remaining 43 control subjects was 4.5 and in the 41 test subjects 2.6 lesions/100 surfaces at risk, i.e. 42% reduction. Caries arrestment had occurred in these test subjects after the first year, while in the respective controls it was continuously increasing. Among numerous oral and body parameters studied, only surface enamel fluoride in primary teeth was increased by the fluoride supplements and urinary phosphate and calcium excretion decreased.

Adolescent↗