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.
D000818:Animals; D001485:Basement Membrane; D002454:Cell Differentiation / Q000187:drug effects; D046508:Culture Techniques; D003810:Dentinogenesis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005944:Glucosamine / Q000031:analogs & derivatives*; D006023:Glycoproteins / Q000096:biosynthesis*; D006025:Glycosaminoglycans / Q000096:biosynthesis; D051379:Mice; D009024:Morphogenesis / Q000187:drug effects; D009804:Odontoblasts / Q000166:cytology*; D009805:Odontogenesis / Q000187:drug effects*; D014083:Tooth Germ / Q000378:metabolism; D014415:Tunicamycin / Q000494:pharmacology*
D006023:Glycoproteins; D006025:Glycosaminoglycans; D014415:Tunicamycin; D005944:Glucosamine