Original scientific paper
https://doi.org/10.18054/pb.v121-122i1-2.10718
Epigenetic drug 5-azacytidine impairs the potential for odontogenesis but improves tooth morphogenesis in the transplanted embryonic mandible
Vedran Radujković
; 1Community healthcare centre “Zagreb-Centar”; 2Department of Histology and Embryology, School of Medicine, 10000 Zagreb, Croatia
Marta Himelreich Perić
orcid.org/0000-0002-2143-6968
; Scool of medicine, University of Zagreb
Marta Takahashi
; 2Department of Histology and Embryology, School of Medicine, 10000 Zagreb, Croatia
Nino Sinčić
orcid.org/0000-0003-2584-6654
; 3University of Zagreb, School of Medicine, Department of Medical Biology, 1000 Zagreb, Croatia; 4Centre of Excellence for Reproductive and Regenerative Medicine, Unit for Biomedical Investigation of Reproduction and Development, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Ana Katušić Bojanac
; 3University of Zagreb, School of Medicine, Department of Medical Biology, 1000 Zagreb, Croatia; 4Centre of Excellence for Reproductive and Regenerative Medicine, Unit for Biomedical Investigation of Reproduction and Development, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Davor Ježek
; 2Department of Histology and Embryology, School of Medicine, 10000 Zagreb, Croatia, 4Centre of Excellence for Reproductive and Regenerative Medicine, Unit for Biomedical Investigation of Reproduction and Development, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Gordana Jurić-Lekić
; 2Department of Histology and Embryology, School of Medicine, 10000 Zagreb, Croatia,4Centre of Excellence for Reproductive and Regenerative Medicine, Unit for Biomedical Investigation of Reproduction and Development, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Floriana Bulić-Jakuš
orcid.org/0000-0002-5538-4692
; 3University of Zagreb, School of Medicine, Department of Medical Biology, 1000 Zagreb, Croatia; 4Centre of Excellence for Reproductive and Regenerative Medicine, Unit for Biomedical Investigation of Reproduction and Development, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
Abstract
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.
Keywords
Hrčak ID:
254650
URI
Publication date:
30.12.2020.
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