Glucose uptake mediated by glucose transporter 1 is essential for early tooth morphogenesis and size determination of murine molars

摘要

Glucoseisanessentialsourceofenergyforbodymetabolismandistransportedintocellsbyglucosetransporters(GLUTs).Well-characterizedclassIGLUTissubdividedintoGLUTs1ndash;4,whichareselectivelyexpresseddependingontissueglucoserequirements.However,thereisnoavailabledataontheroleofGLUTsduringtoothdevelopment.ThisstudyaimstoclarifythefunctionalsignificanceofclassIGLUTduringmurinetoothdevelopmentusingimmunohistochemistryandaninvitroorgancultureexperimentwithaninhibitorofGLUTs1/2,phloretin,andemGlut1/emandemGlut2/emshortinterferingRNA(siRNA).AnintenseGLUT1-immunoreactionwaslocalizedintheenamelorganofbud-stagemolartoothgerms,wheretheactivecellproliferationoccurred.Bythebellstage,theexpressionofGLUT1inthedentalepitheliumwasdramaticallydecreasedinintensity,andsubsequentlybegantoappearinthestratumintermediumatthelatebellstage.Ontheotherhand,GLUT2-immunoreactivitywasweaklyobservedinthewholetoothgermsthroughoutallstages.TheinhibitionofGLUTs1/2byphloretininthebud-stagetoothgermsinducedthedisturbanceofprimaryenamelknotformation,resultinginthedevelopmentalarrestoftheexplantsandthesquamousmetaplasiaofdentalepithelialcells.Furthermore,theinhibitionofGLUTs1/2incap-to-bell-stagetoothgermsreducedtoothsizeinadosedependentmanner.ThesefindingssuggestthattheexpressionofGLUT1andGLUT2inthedentalepithelialandmesenchymalcellsseemstobepreciselyandspatiotemporallycontrolled,andtheglucoseuptakemediatedbyGLUT1playsacrucialroleintheearlytoothmorphogenesisandtoothsizedetermination./p/div