engleski

Epigenetic drug 5-azacytidine impairs the potential for odontogenesis but improves tooth morphogenesis in the transplanted embryonic mandible

Background and purpose: Epigenetic mechanisms are crucial in regulating development. The aim of the study was to investigate whether a DNA demethylation drug 5-azacytidine (5azaC) affects odontogenesis in embryonic mandibles ectopically transplanted in vivo. Materials and methods: Mandibles from 13.5- and 14.5-day-old Fischer rat embryos containing early tooth- primordia (dental laminas) were transplanted under the kidney capsule of adult males. Host animals were treated with 5azaC(5mg/kg, i.p.) for the first three days and sham controls with PBS. After two weeks, differentiation was analysed by histology and cell proliferation by immunohistochemistry. Results: In some transplants, the bell stage of incisors and molars developed. Teeth in 13.5-day-old transplants produced only dentine, and the incidence of mandibles with teeth in 5azaC treated hosts was lower. PCNA was expressed only in odontoblasts. Several 14.5-day-old transplants developed teeth with both dentine and enamel. In 5azaC-treated hosts, Hertwig’s epithelial root sheath developed, but the number of mandibles with teeth was lower than in controls (p˂0.05. Somewhat fewer molars than incisors developed under 5azaC-treatment. Differentiation of the bone, cartilage, salivary glands, epidermis, hair, sebaceous glands, and adipose cells proceeded in all transplants, except for myotubes that were absent from older transplanted mandibles. Conclusions: Embryonic mandibles retained the potential for the development of teeth at the ectopic site, but odontogenesis was more advanced in a-day-older mandibles. In older mandibles, the 5-azaC impaired potential for odontogenesis, but teeth that developed reached a higher stage of organogenesis. These results are contributing to the epigenetic explanation of the development of teeth anomalies.

tooth ; anomalies ; Vidaza ; embryo ; grafting ; epigenetics ; DNA-methylation

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