title: Circadian rhythms regulate amelogenesis.
abstract: Ameloblasts, the cells responsible for making enamel, modify their morphological features in response to specialized functions necessary for synchronized ameloblast differentiation and enamel formation. Secretory and maturation ameloblasts are characterized by the expression of stage-specific genes which follows strictly controlled repetitive patterns. Circadian rhythms are recognized as key regulators of the development and diseases of many tissues including bone. Our aim was to gain novel insights on the role of clock genes in enamel formation and to explore the potential links between circadian rhythms and amelogenesis. Our data shows definitive evidence that the main clock genes (Bmal1, Clock, Per1 and Per2) oscillate in ameloblasts at regular circadian (24 h) intervals both at RNA and protein levels. This study also reveals that the two markers of ameloblast differentiation i.e. amelogenin (Amelx; a marker of secretory stage ameloblasts) and kallikrein-related peptidase 4 (Klk4, a marker of maturation stage ameloblasts) are downstream targets of clock genes. Both, Amelx and Klk4 show 24h oscillatory expression patterns and their expression levels are up-regulated after Bmal1 over-expression in HAT-7 ameloblast cells. Taken together, these data suggest that both the secretory and the maturation stages of amelogenesis might be under circadian control. Changes in clock gene expression patterns might result in significant alterations of enamel apposition and mineralization.
authors.affiliation: Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.forename: Yoon Ji
authors.initials: YJ
authors.lastname: Seon
authors.forename: Marcio A
authors.initials: MA
authors.lastname: Mourão
authors.forename: Santiago
authors.initials: S
authors.lastname: Schnell
authors.forename: Doohak
authors.initials: D
authors.lastname: Kim
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Harada
authors.forename: Silvana
authors.initials: S
authors.lastname: Papagerakis
authors.forename: Petros
authors.initials: P
authors.lastname: Papagerakis
mesh_terms: D056930:ARNTL Transcription Factors / Q000235:genetics / Q000378:metabolism; D000565:Ameloblasts / Q000378:metabolism; D000566:Amelogenesis / Q000235:genetics; D053523:Amelogenin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D056926:CLOCK Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002940:Circadian Rhythm / Q000235:genetics; D005583:Fourier Analysis; D005786:Gene Expression Regulation; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000235:genetics; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D056930:ARNTL Transcription Factors; D053523:Amelogenin; C507200:Amelx protein, mouse; C538961:Bmal1 protein, mouse; D012333:RNA, Messenger; D056926:CLOCK Proteins; D007610:Kallikreins; C120801:kallikrein 4