RESUMEN
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.
Asunto(s)
Animales , Humanos , Ratones , Ratas , Fenómenos Biomecánicos , Western Blotting , Remodelación Ósea , Células Cultivadas , Transportador de Glucosa de Tipo 1 , Genética , Hidroxibenzoatos , Farmacología , Inmunohistoquímica , Sistema de Señalización de MAP Quinasas , Ratones Endogámicos C57BL , Osteoprotegerina , Metabolismo , Ligamento Periodontal , Biología Celular , Ligando RANK , Metabolismo , Ratas Sprague-Dawley , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Técnicas de Movimiento Dental , Activación TranscripcionalRESUMEN
Objective To explore the clinical curative effect of acute pancreatitis by octreotide and anisodamine. Methods Eighty cases acute pancreatitis in our hospital were analyzed,were divided into two groups,the control group 30 cases and observation group 50 cases. Results The general information on sex、age、 duration of disease distribution of acute pancreatitis two groups had no difference (P>0.05),the abdominal pain relief time、 serum amylase、 urine amylase、hospitalization time of acute pancreatitis of observation group was better than control group , the CPR、TNF-α、IL-4、IL-8、IL-10 and clinical treatment efficiency of acute pancreatitis of observation group was better than control group (P<0.05),the differences were statistically significanct. Conclusion The clinical symptom of acute pancreatitis by octreotide combined with anisodamine is obviously improved ,clinical therapeutic effect is increased.