Abstract
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.
Highlights
The tissue microenvironment, including the extracellular matrix and three-dimensional geometrics, imposes physical constraints on solid tissues.[1,2] These physical cues affect numerous cellular processes, such as cell differentiation and proliferation, through widespread crosstalk with various signalling cascades.[3,4,5,6,7] Despite the vital importance of metabolism to life, little is known about its interaction with mechanoresponses
Functional interaction between glucose transporter 1 (GLUT1) and ERK pathway in mechanotransduction To unveil the functional interaction between GLUT1-mediated nutrient assimilation and physical strain-elicited stress response in periodontal ligament cells (PDLCs), we focused on MAPK/ERK cascades
In this study, we demonstrated that mechanical force could induce GLUT1 expression in both an in vivo orthodontic tooth movement (OTM) model and in vitro cultured human PDLCs stressed with compressive force, and this regulation contributed to osteoclast differentiation in periodontal tissue remodelling
Summary
The tissue microenvironment, including the extracellular matrix and three-dimensional geometrics, imposes physical constraints on solid tissues.[1,2] These physical cues affect numerous cellular processes, such as cell differentiation and proliferation, through widespread crosstalk with various signalling cascades.[3,4,5,6,7] Despite the vital importance of metabolism to life, little is known about its interaction with mechanoresponses. We use a combination of OTM models both in vivo linked to mechanoresponse in a pilot experiment To validate this and in vitro to demonstrate the novel and universal upregulation of point in an in vivo setting, we established a rat OTM model by GLUT1 by mechanical stimuli. Histopathological examination of strained underlying molecular mechanisms These results together highlight rats revealed a concentrated Glut[1] staining pattern along the the significance of the transcriptional activation of GLUT1 as a key boundary of the PDL and indicated a large fraction of cells with component linking metabolism and bone homoeostasis.
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