title: Exposure to a continuous low dose of tetrachlorodibenzo-p-dioxin impairs the development of the tooth root in lactational rats and alters the function of apical papilla-derived stem cells.
abstract: OBJECTIVE
  Ubiquitous environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) cause abnormalities in reproduction and development. TCDD inhibits the development of teeth, and its effects depend on its dose and the developmental stage of the tooth. Our aim here was to investigate the effect of lower doses of TCDD on the development of the tooth root in vivo and in vitro.
  
  
  METHODS
  We observed tooth root development in lactational rats exposed to continuous low doses of TCDD starting on postnatal day 6 using Mico-CT analyses and histopathological examinations. And then the characteristics of stem cells derived from the apical papilla (SCAPs) were evaluated and compared with SCAPs induced by lower doses of TCDD both in vitro and in vivo.
  
  
  RESULTS
  The results of experiments showed that rat pups exposed to low dose TCDD at prenatal stage developed, dentine hypoplasia, and hypomineralization. Further, TCDD impaired the functions of SCAPs in vivo by inhibiting cell proliferation and osteogenic and odontogenic differentiation. The impairment of SCAPs after TCDD exposure was accompanied by increased expression of AHR, down-regulation of the expression of Runx2, and alkaline phosphatase, suggesting that the AHR pathway mediated the effects of TCDD.
  
  
  CONCLUSIONS
  These results provide the first insights into the toxicity of TCDD, which adversely affects the development of the tooth root through indirectly altering the function of SCAPs.
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Military Stomatology, Research and Development Center for Tissue Engineering, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Dentistry, Hospital of Dangdu, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Kewen
authors.initials: K
authors.lastname: Wei
authors.affiliation: Department of Aerospace Biodynamics, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Jiangdong
authors.initials: J
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Yurui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China. Electronic address: jinfang@fmmu.edu.cn.
authors.forename: Fang
authors.initials: F
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Military Stomatology, Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China. Electronic address: xuankun@fmmu.edu.cn.
authors.forename: Kun
authors.initials: K
authors.lastname: Xuan
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D015703:Antigens, CD / Q000378:metabolism; D049109:Cell Proliferation; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D007774:Lactation / Q000187:drug effects*; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010641:Phenotype; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects*; D014092:Tooth Root / Q000000981:diagnostic imaging / Q000187:drug effects*; D055114:X-Ray Microtomography
chemical_list: D015703:Antigens, CD; D050659:Core Binding Factor Alpha 1 Subunit; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; C493717:Runx2 protein, rat; D000469:Alkaline Phosphatase
keywords: SCAPs; TCDD; Teeth roots development