Transcriptional activation of glucose transporter 1 in orthodontic tooth movement-associated mechanical response

• Main Authors: Jin, S. (Author), Li, Q. (Author), Liu, F. (Author), Wang, Y. (Author), Zhang, T. (Author), Zhang, Y. (Author), Zhou, Y. (Author), Zhu, Y. (Author)
• Format: Article
• Language: English
• Published: Sichuan University Press 2018
• Subjects: animal; Animals; antagonists and inhibitors; Biomechanical Phenomena; biomechanics; Blotting, Western; bone remodeling; Bone Remodeling; C57BL mouse; cell culture; Cells, Cultured; cytology; drug effect; genetics; glucose transporter 1; Glucose Transporter Type 1; human; Humans; Hydroxybenzoates; hydroxybenzoic acid derivative; immunohistochemistry; Immunohistochemistry; MAP Kinase Signaling System; MAPK signaling; metabolism; Mice; Mice, Inbred C57BL; mouse; orthodontic tooth movement; osteoclast differentiation factor; osteoprotegerin; Osteoprotegerin; periodontal ligament; Periodontal Ligament; RANK Ligand; rat; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; reverse transcription polymerase chain reaction; Sprague Dawley rat; Tooth Movement Techniques; transcription initiation; Transcriptional Activation; Western blotting; WZB117
• Online Access: View Fulltext in Publisher

 The interplay between mechanoresponses and a broad range of fundamental biological processes, such as cell cycle progression, growth and differentiation, has been extensively investigated. However, metabolic regulation in mechanobiology remains largely unexplored. Here, we identified glucose transporter 1 (GLUT1)—the primary glucose transporter in various cells—as a novel mechanosensitive gene in orthodontic tooth movement (OTM). Using an in vivo rat OTM model, we demonstrated the specific induction of Glut1 proteins on the compressive side of a physically strained periodontal ligament. This transcriptional activation could be recapitulated in in vitro cultured human periodontal ligament cells (PDLCs), showing a time- and dose-dependent mechanoresponse. Importantly, application of GLUT1 specific inhibitor WZB117 greatly suppressed the efficiency of orthodontic tooth movement in a mouse OTM model, and this reduction was associated with a decline in osteoclastic activities. A mechanistic study suggested that GLUT1 inhibition affected the receptor activator for nuclear factor-κ B Ligand (RANKL)/osteoprotegerin (OPG) system by impairing compressive force-mediated RANKL upregulation. Consistently, pretreatment of PDLCs with WZB117 severely impeded the osteoclastic differentiation of co-cultured RAW264.7 cells. Further biochemical analysis indicated mutual regulation between GLUT1 and the MEK/ERK cascade to relay potential communication between glucose uptake and mechanical stress response. Together, these cross-species experiments revealed the transcriptional activation of GLUT1 as a novel and conserved linkage between metabolism and bone remodelling. © 2018, The Author(s).