Glucose Transporter 1 Modulates Orthodontic Tooth Movement by Osteoclastic Cascade

Objectives: To investigate the interplay between stress-induced transcriptional alteration of GlUT1 and orthodontic tooth movement as well as molecular mechanisms in the process
Methods: A classical orthodontic tooth movement（OTM）model was utilized to detect the transcriptional alteration of GlUT1 by mechanical stress. Western blot and Real-time PCR were employed to investigate GLUT1 mRNA and protein expression in in vitro simulative mechanics micro environment. WZB117, that served as a familiar specific inhibitor, was administrated intraperitoneally to illuminate the association between potentiated GLUT1 activation and osteoclastic activity as a proverbial concomitant of OTM. Molecular mechanism of GLUT1’ s involvement in OTM was further explored by mechanical stress loading setup in vitro.
Results: We identified that GLUT1’s transcription were activated on the pressure side of mechanically stretched periodontal ligament . Alternatively, this phenomenon could be recapitulated in in vitro human periodontal ligament cells (PDLC), rendering a time- and dose- dependent manifestation. Moreover , administration of GLUT1 specific inhibitor WZB117 remarkably casted down the osteoclastic activities , thus restraining the progress of orthodontic tooth movement . In vitro cell experiment suggested that GLUT1 suppression disturbed RANKL/OPG system by damnifying pressured-mediated RANKL elevation. Correspondingly , pretreatment of PDLCs with WZB117 seriously hindered osteoclastic differentiation of co-cultured RAW264.7 cells. Furthermore , an interactional modulation between GLUT1 and MEK/ERK pathway were corroborated , throwing lighting on the unmentioned reciprocation between glucose uptake and mechanical stress
Conclusions: Our findings suggest that transcriptional activation of GLUT1 in all likelihood facilitates the osteoclastic differentiation in the bone remodeling of the pressure side, thus modulating the process of OTM. More importantly, our exploration illuminates an intriguing molecular mechanism by which OTM is regulated by force-induced transcriptional alteration of GLUT1 from metabolism perspective