Circadian Rhythm Regulates Mouse Enamel Mineralization Via Melatonin-BMAL1-JNK3

This study aims to determine whether circadian rhythm regulates enamel mineralization through the melatonin-Bmal1-Jnk3 pathway by establishing a circadian rhythm-disrupted mouse model, combined with molecular pathway detection and morphological observation of enamel. BALB/c pregnant mice were randomly divided into three groups: control group (12 hours of light/day), high-light group (16 hours of light/day), continuous-light group (24 hours of light/day). RT-qPCR was used to detect the expression levels of Bmal1, Arrb1 and Amelx in the tooth germs of 3-day-old mice, and the 24-hour variation curves of gene expression in the control and high-light groups were plotted. ELISA was used to measure the 24-hour melatonin concentration changes in 3-day-old mice. 3D X-ray microscopy was used to observe enamel development in the mandibular molars of 3-week-old mice, with enamel thickness and density measured. Gene expression in the tooth germs of mice with circadian rhythm disruption was suppressed. The diurnal oscillation patterns of Bmal1, Arrb1 and Amelx showed significant synchronization with serum melatonin concentration fluctuations. In 3-week-old mice from the continuous-light and high-light groups, the average enamel thickness and density of mandibular molars decreased, and the maximum enamel thickness was significantly reduced compared to the control group. Circadian rhythm regulates the developmental mineralization of mouse tooth enamel via melatonin-BMAL1-JNK3. Circadian rhythm disruption may lead to abnormal Bmal1 expression by affecting melatonin secretion, thereby impairing normal enamel mineralization.