LAUSR

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.Orthodontics: Glucose transport needed to straighten teethA glucose-transporting protein is key to helping teeth respond to orthodontic implants, say researchers in China. Implants apply forces to teeth and the periodontal ligament (PDL) that holds them in place, causing bone to grow on one side and be absorbed into the body on the other. Yanheng Zhou and co-workers at Peking University in Beijing showed that GLUT1, a protein that transports glucose through cell membranes, was greatly upregulated in rat, mouse and human PDL cells subjected to mechanical force. They also injected some of the mice with a GLUT1 inhibitor and found that the treatment greatly decreased the distance moved by the teeth. This could be attributed to a decline in the activity of cells that break down bone tissue and a failure in signalling channels when GLUT1 is inhibited.