Hao Guo1, Liqiang Zhang2, Kewen Wei3, Jiangdong Zhao4, Yurui Wang1, Fang Jin5, Kun Xuan6. 1. 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. 2. 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. 3. Department of Dentistry, Hospital of Dangdu, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China. 4. Department of Aerospace Biodynamics, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China. 5. 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. 6. 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.
Abstract
OBJECTIVES: 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. DESIGN: 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. CONCLUSION: 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.
OBJECTIVES: 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. DESIGN: 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. CONCLUSION: 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: Chawon Yun; Karina M Katchko; Michael S Schallmo; Soyeon Jeong; Jonghwa Yun; Charlotte H Chen; Joseph A Weiner; Christian Park; Andrew George; Samuel I Stupp; Wellington K Hsu; Erin L Hsu Journal: Int J Mol Sci Date: 2018-01-11 Impact factor: 5.923
Authors: Chawon Yun; Joseph A Weiner; Danielle S Chun; Jonghwa Yun; Ralph W Cook; Michael S Schallmo; Abhishek S Kannan; Sean M Mitchell; Ryan D Freshman; Christian Park; Wellington K Hsu; Erin L Hsu Journal: Bone Rep Date: 2017-02-16