Jedeon Katia, Loiodice Sophia, Marciano Clémence, Vinel Alexia, Canivenc Lavier Marie-Chantal, Berdal Ariane, Babajko Sylvie
Centre de Recherche des Cordeliers (K.J., S.L., C.M., A.B., S.B), Institut National de la Santé et de la Recherche Médicale UMRS 1138, Laboratory of Molecular Oral Pathophysiology; Université Paris-Descartes (K.J., S.L.C.M.,A.B., S.B.); Université Pierre et Marie Curie-Paris (K.J., S.L., C.M., A.B., S.B); and Université Paris-Diderot (K.J., A.B., S.B.), UFR d'Odontologie, F-75006, Paris, France; I2MC (A.V.), Institut National de la Santé et de la Recherche Médicale U1048, équipe 9 and Université Paul Sabatier (A.V.), 31432 Toulouse, France; Institut National de la Recherche Agronomique UMR 1324 (M.-C.C.L.), Centre des sciences du gout et de l'alimentation - BP 86 510; CNRS UMR 6265 (M.-C.C.L.), Centre des sciences du gout et de l'alimentation; and Université de Bourgogne (M.-C.C.L.), Centre des sciences du gout et de l'alimentation, 21 065 Dijon, France; and Centre de Référence des maladies rares de la face et de la cavité buccale MAFACE hôpital Rothschild (A.B.), AP-HP, 75012 Paris, France.
Endocrinology. 2014 Sep;155(9):3365-75. doi: 10.1210/en.2013-2161. Epub 2014 Jul 8.
Bisphenol A (BPA) is a widespread endocrine disrupting chemical (EDC) strongly suspected to have adverse health effects. Numerous tissues and cells are affected by BPA, and we showed recently that BPA targets include ameloblasts and enamel. We therefore investigated the effects of BPA on ameloblasts and the possible involvement of the estrogen signaling pathway. Rats were exposed daily to low-dose BPA, and developed enamel hypomineralization similar to human molar incisor hypomineralization (MIH). BPA increased ameloblast proliferation in vivo and in vitro. The proliferation of the rat dental epithelial cell line HAT-7 was also increased by estrogen (E2). Ameloblasts express ERα but not ERβ both in vivo and in vitro. The ER antagonist ICI 182,780 was used to inactivate ERα and abolished the effects of E2 on cell proliferation and transcription, but only partially reduced the effects of BPA. In conclusion, we show, for the first time, that: 1) BPA has ER-dependent and ER-independent effects on ameloblast proliferation and gene transcription; 2) the estrogen signaling pathway is involved in tooth development and the enamel mineralization process; and 3) BPA impacts preferentially amelogenesis in male rats. These results are consistent with the steroid hormones having effect on ameloblasts, raising the issues of the hormonal influence on amelogenesis and possible differences in enamel quality between sexes.
双酚A（BPA）是一种广泛存在的内分泌干扰化学物质（EDC），人们强烈怀疑它会对健康产生不良影响。许多组织和细胞都会受到BPA的影响，我们最近发现BPA的作用靶点包括成釉细胞和牙釉质。因此，我们研究了BPA对成釉细胞的影响以及雌激素信号通路可能发挥的作用。大鼠每天暴露于低剂量BPA中，会出现类似于人类磨牙釉质矿化不全（MIH）的牙釉质矿化不全。BPA在体内和体外均可增加成釉细胞的增殖。雌激素（E2）也可增加大鼠牙上皮细胞系HAT-7的增殖。成釉细胞在体内和体外均表达雌激素受体α（ERα），但不表达雌激素受体β（ERβ）。使用ER拮抗剂ICI 182,780使ERα失活，可消除E2对细胞增殖和转录的影响，但只能部分降低BPA的作用。总之，我们首次表明：1）BPA对成釉细胞增殖和基因转录具有ER依赖性和非ER依赖性作用；2）雌激素信号通路参与牙齿发育和牙釉质矿化过程；3）BPA对雄性大鼠的釉质形成影响更为明显。这些结果与类固醇激素对成釉细胞有作用一致，这也引发了激素对釉质形成的影响以及两性牙釉质质量可能存在差异的问题。
