Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars.
Glucose is an essential source of energy for body metabolism and is transported into cells by glucose transporters (GLUTs). Well-characterized class I GLUT is subdivided into GLUTs1-4, which are selectively expressed depending on tissue glucose requirements. However, there is no available data on the role of GLUTs during tooth development. This study aims to clarify the functional significance of class I GLUT during murine tooth development using immunohistochemistry and an in vitro organ culture experiment with an inhibitor of GLUTs1/2, phloretin, and Glut1 and Glut2 short interfering RNA (siRNA). An intense GLUT1-immunoreaction was localized in the enamel organ of bud-stage molar tooth germs, where the active cell proliferation occurred. By the bell stage, the expression of GLUT1 in the dental epithelium was dramatically decreased in intensity, and subsequently began to appear in the stratum intermedium at the late bell stage. On the other hand, GLUT2-immunoreactivity was weakly observed in the whole tooth germs throughout all stages. The inhibition of GLUTs1/2 by phloretin in the bud-stage tooth germs induced the disturbance of primary enamel knot formation, resulting in the developmental arrest of the explants and the squamous metaplasia of dental epithelial cells. Furthermore, the inhibition of GLUTs1/2 in cap-to-bell-stage tooth germs reduced tooth size in a dose dependent manner. These findings suggest that the expression of GLUT1 and GLUT2 in the dental epithelial and mesenchymal cells seems to be precisely and spatiotemporally controlled, and the glucose uptake mediated by GLUT1 plays a crucial role in the early tooth morphogenesis and tooth size determination.
Division of Anatomy and Cell Biology of the Hard Tissue, Department of Tissue Regeneration and Reconstruction, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8514, Japan.
Hiroko
H
Ida-Yonemochi
Mitsushiro
M
Nakatomi
Hidemitsu
H
Harada
Hiroki
H
Takata
Otto
O
Baba
Hayato
H
Ohshima
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004658:Enamel Organ / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005947:Glucose / Q000493:pharmacokinetics*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism*; D051273:Glucose Transporter Type 2 / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008963:Molar / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D009805:Odontogenesis; D010693:Phloretin / Q000494:pharmacology; D011247:Pregnancy; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D046509:Tissue Culture Techniques; D014083:Tooth Germ / Q000196:embryology / Q000254:growth & development / Q000378:metabolism
D051272:Glucose Transporter Type 1; D051273:Glucose Transporter Type 2; C495678:Slc2a1 protein, mouse; C495682:Slc2a2 protein, mouse; D005947:Glucose; D010693:Phloretin