title: Circadian Rhythm Regulates Development of Enamel in Mouse Mandibular First Molar.
abstract: Rhythmic incremental growth lines and the presence of melatonin receptors were discovered in tooth enamel, suggesting possible role of circadian rhythm. We therefore hypothesized that circadian rhythm may regulate enamel formation through melatonin receptors. To test this hypothesis, we examined expression of melatonin receptors (MTs) and amelogenin (AMELX), a maker of enamel formation, during tooth germ development in mouse. Using qRT-PCR and immunocytochemistry, we found that mRNA and protein levels of both MTs and AMELX in normal mandibular first molar tooth germs increased gradually after birth, peaked at 3 or 4 day postnatal, and then decreased. Expression of MTs and AMELX by immunocytochemistry was significantly delayed in neonatal mice raised in all-dark or all-light environment as well as the enamel development. Furthermore, development of tooth enamel was also delayed showing significant immature histology in those animals, especially for newborn mice raised in all daylight condition. Interestingly, disruption in circadian rhythm in pregnant mice also resulted in delayed enamel development in their babies. Treatment with melatonin receptor antagonist 4P-PDOT in pregnant mice caused underexpression of MTs and AMELX associated with long-lasting deficiency in baby enamel tissue. Electromicroscopic evidence demonstrated increased necrosis and poor enamel mineralization in ameloblasts. The above results suggest that circadian rhythm is important for normal enamel development at both pre- and postnatal stages. Melatonin receptors were partly responsible for the regulation.
authors: Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Jiang
authors: J
authors: Tao
authors: Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Yue
authors: Y
authors: Zhai
authors: Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Hyun
authors: H
authors: Park
authors: Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Junli
authors: J
authors: Han
authors: Department of General Dentistry, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Jianhui
authors: J
authors: Dong
authors: Department of Prosthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Ming
authors: M
authors: Xie
authors: Department of Oral Pathology, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Ting
authors: T
authors: Gu
authors: Department of Medicine, Windsor University School of Medicine, St. Kitts & Nevis.
authors: Keidren
authors: K
authors: Lewi
authors: Department of Orthodontics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Key Laboratory of Stomatology, Shanghai, China.
authors: Fang
authors: F
authors: Ji
authors: Brain Research Centre, Department of Surgery, University of British Columbia, Canada.
authors: William
authors: W
authors: Jia
mesh_terms: D000565:Ameloblasts / Q000166:cytology / Q000378:metabolism; D053523:Amelogenin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002940:Circadian Rhythm / Q000502:physiology* / Q000528:radiation effects; D003743:Dental Enamel / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D003746:Dental Enamel Proteins / Q000235:genetics; D005260:Female; D007150:Immunohistochemistry; D008027:Light; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D008963:Molar / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D060888:Real-Time Polymerase Chain Reaction; D044094:Receptors, Melatonin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014083:Tooth Germ / Q000378:metabolism / Q000473:pathology
chemical_list: C114459:4-phenyl-2-propionamidotetraline; D053523:Amelogenin; D003746:Dental Enamel Proteins; D044094:Receptors, Melatonin; D013764:Tetrahydronaphthalenes