Effect and potential mechanism of p75NTR in the regulation of the circadian rhythm and daily mineralization during tooth development

Abstract

Abstract Circadian rhythms are innate processes that are responsive to light/dark cycles and participate in the regulation of various physiological functions. Mammalian teeth provide a precise record of these rhythms through the incremental growth lines in the dentine and enamel. The aim of this study was to identify the effect and potential mechanism of p75 neurotrophin receptor (p75NTR) in the regulation of the circadian rhythm and daily mineralization during tooth development. p75NTR expression was found to be similar to that of the clock genes and mineralization-related factors in rat dental germs. The significant decreases in the body size and weight of p75NTR knock-out mice indicated that p75NTR might promote osteogenesis. p75NTR showed close positive relationships with melatonin, crown length, eruption speed, and daily mineralization width. In the circadian rhythm dynamics of rat dental germs study, p75NTR oscillated regularly at an approximately 24-hour interval, at both the mRNA and protein levels; this was similar to most clock genes (Bmal1, Clock, Per1, and Per2), mineralization-related genes (Runx2, ALP), and odontogenesis-related genes (Msx1, Dlx1, Dmp1 and Dspp). Moreover, p75NTR displayed positive relationships with clock, mineralization-related, and odontogenesis-related genes in both the over-expression and knockdown experiments. These data reveal that p75NTR promotes the crown length, eruption speed, and daily mineralization width and significantly affects the circadian rhythm and periodic mineralization during tooth development. Furthermore, CK2 was found to be a possible downstream factor of p75NTR; however, direct bonding between CK2 and p75NTR was not observed. Further studies are needed to verify these findings.