TY - JOUR
T1 - HIF-2α Inhibits Ameloblast Differentiation via Hey2 in Tooth Development
AU - Kimura, S.
AU - Takeshita, N.
AU - Oyanagi, T.
AU - Seki, D.
AU - Jiang, W.
AU - Hidaka, K.
AU - Fukumoto, S.
AU - Takahashi, I.
AU - Takano-Yamamoto, T.
N1 - Funding Information:
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This study was supported by a Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (19K24085 to S. Kimura, 18K17241 and 21K17175 to T. Oyanagi, and 15H05048 to T. Takano-Yamamoto).
Publisher Copyright:
© International Association for Dental Research and American Association for Dental, Oral, and Craniofacial Research 2022.
PY - 2022/12
Y1 - 2022/12
N2 - Enamel is the highly mineralized outer layer of teeth; the cells responsible for enamel formation are ameloblasts. Local hypoxia and hypoxia inducible factor (HIF) in embryonic tissues are important to promote normal organogenesis. However, hypoxic state in tooth germs and the roles of HIF in ameloblast differentiation have not been understood. The aim of this study is to clarify the role of HIF in ameloblast differentiation during tooth germ development. We found that tooth germs were under hypoxia and HIF-1α and HIF-2α were expressed in tooth germs in embryonic mice. Then, we used HIF inhibitors to evaluate the function of HIF during tooth germ development. The HIF-2α inhibitor significantly decreased the size of tooth germs in organ culture, while the HIF-1α inhibitor did not apparently affect the size of tooth germs. The HIF-2α inhibitor enhanced the expression of amelogenin, a marker of ameloblast differentiation, in the tooth germs in organ culture and rat dental epithelial SF2 cells. Moreover, we found that the HIF-2α inhibitor-stimulating amelogenin expression was regulated by hes-related family basic helix-loop-helix transcription factor with YRPW motif 2(Hey2) in SF2 cells. These findings suggest that the HIF-2α–Hey2 axis plays an important role in ameloblast differentiation during tooth germ development.
AB - Enamel is the highly mineralized outer layer of teeth; the cells responsible for enamel formation are ameloblasts. Local hypoxia and hypoxia inducible factor (HIF) in embryonic tissues are important to promote normal organogenesis. However, hypoxic state in tooth germs and the roles of HIF in ameloblast differentiation have not been understood. The aim of this study is to clarify the role of HIF in ameloblast differentiation during tooth germ development. We found that tooth germs were under hypoxia and HIF-1α and HIF-2α were expressed in tooth germs in embryonic mice. Then, we used HIF inhibitors to evaluate the function of HIF during tooth germ development. The HIF-2α inhibitor significantly decreased the size of tooth germs in organ culture, while the HIF-1α inhibitor did not apparently affect the size of tooth germs. The HIF-2α inhibitor enhanced the expression of amelogenin, a marker of ameloblast differentiation, in the tooth germs in organ culture and rat dental epithelial SF2 cells. Moreover, we found that the HIF-2α inhibitor-stimulating amelogenin expression was regulated by hes-related family basic helix-loop-helix transcription factor with YRPW motif 2(Hey2) in SF2 cells. These findings suggest that the HIF-2α–Hey2 axis plays an important role in ameloblast differentiation during tooth germ development.
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U2 - 10.1177/00220345221111971
DO - 10.1177/00220345221111971
M3 - Article
C2 - 35912776
AN - SCOPUS:85135400373
SN - 0022-0345
VL - 101
SP - 1637
EP - 1644
JO - Journal of Dental Research
JF - Journal of Dental Research
IS - 13
ER -