title: Maternal diabetes modulates offspring cell proliferation and apoptosis during odontogenesis via the TLR4/NF-κB signalling pathway.
abstract: OBJECTIVE
  Maternal gestational diabetes leads to an adverse in utero environment and increases the risk of malformations during embryo organogenesis. In the present study, we analysed the effects of maternal diabetes on tooth germ cell proliferation and apoptosis in offspring, and investigated their underlying mechanisms.
  
  
  METHODS
  A rat model of maternal diabetes was induced by intraperitoneal injection of streptozotocin and the pregnant rats were divided into three groups: controls, the diabetic group and diabetic group with insulin treatment. Offspring of the three groups were collected and cell proliferation and apoptosis in tooth germs were analysed. Primary dental papilla cells and dental epithelial stem cells were isolated and treated with high glucose in vitro, in an attempt to simulate maternal diabetes-induced hyperglycaemia in vivo.
  
  
  RESULTS
  Maternal diabetes significantly affected cell proliferation and apoptosis in offspring tooth germs. The TLR4/NF-ĸB signalling pathway was activated in the tooth germs of offspring of diabetic dams. High glucose treatment activated the TLR4/NF-ĸB signalling pathway in primary dental papilla cells and dental epithelial stem cells in vitro, resulting in suppression of cell proliferation and enhancement of apoptosis. TLR4 knockdown significantly reduced adverse effects induced by high glucose treatment.
  
  
  CONCLUSIONS
  Maternal gestational diabetes significantly impaired dental epithelial and mesenchymal cell proliferation and apoptosis in offspring, possibly by activation of the TLR4/NF-ĸB signalling pathway.
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.|National Engineering Laboratory for Oral Regenerative Medicine, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.|National Engineering Laboratory for Oral Regenerative Medicine, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.|National Engineering Laboratory for Oral Regenerative Medicine, West China College of Stomatology, Sichuan University, Chengdu, China.|Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.|National Engineering Laboratory for Oral Regenerative Medicine, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.|National Engineering Laboratory for Oral Regenerative Medicine, West China College of Stomatology, Sichuan University, Chengdu, China.|Department of Pedodontics, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Oral Diseases, West China College of Stomatology, Sichuan University, Chengdu, China.|National Engineering Laboratory for Oral Regenerative Medicine, West China College of Stomatology, Sichuan University, Chengdu, China.|Department of Oral and Maxillofacial Surgery, West China College of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Tian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016640:Diabetes, Gestational / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism*; D009805:Odontogenesis; D011247:Pregnancy; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013311:Streptozocin / Q000008:administration & dosage; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D007328:Insulin; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D013311:Streptozocin
keywords: TLR4/NF-ĸB signalling; apoptosis; cell proliferation; maternal diabetes; tooth development