Chronodentistry: The Role & Potential of Molecular Clocks in Oral Medicine

Klara Janjić; Hermann Agis

Disclosures

BMC Oral Health. 2019;19(32) 

In This Article

Discussion

The basis for chronodentistry has been set by demonstrating that dental pulp,[84] periodontal tissues,[11] oral mucosa,[44] enamel,[50] dentin[85] and mandibular bone[36] show clear evidence for the presence of peripheral clocks by producing its core components (Table 1). Specific functions of respective peripheral clocks in oral tissues and the mechanisms that are implied on the way to the fulfillment of such a function or behavior are still widely unknown. Meanwhile a dysfunctional clock mechanism has been attributed to be involved in the development of oral cancer[31–34] and juvenile skeletal mandibular hypoplasia.[36] Another step to put the pieces together is to find clock-controlled genes. A number of genes involved in oral biology were suggested to be produced in a circadian rhythm, but be careful when indicating a circadian pattern behind the production of genes or proteins. Except for so-called housekeeping genes and proteins, most gene expressions will show variances in production levels over the day, but this is by far not enough evidence to claim a circadian clock mechanism behind it. One of the most important characteristics of a circadian clock mechanism is that there is no action-reaction process, but a training process. Thus, entrainment status has to be assessed in free-running experiments, where the external stimulus is put away after a certain training period and the oscillation pattern still would be present. Taken together, a circadian clock mechanism has to be based on a repeating oscillation pattern, an entrainment by an environmental cue and free-running experiments (Figure 3). Significant results should be supported not only by training, but also synchronization and determining oscillation patterns as well as cell cycle stages before and after training and synchronization.

Figure 3.

Circadian clock hallmarks. A functional circadian clock has to include three characteristics: gene or protein production has to follow an oscillation pattern over approximately 24 h, the circadian rhythm is entrained by an environmental stimulus (zeitgeber [official technical term]) and continues with its oscillation pattern, even after taking away the stimulus

Chronodentistry is still some steps away from patient application, but already shows potential in the different fields of dentistry including restorative dentistry, endodontics, periodontics, orthodontics and oral and maxillofacial surgery. The field of pediatric dentistry has not been covered yet on any aspect of the circadian clock. Although, it would be interesting if genes that are involved in tooth development, change from deciduous to permanent dentition or development of oral pediatric disorders are clock-controlled and display circadian behavior. Particularly for children, non-invasive treatment approaches as light therapy are desirable. Light being the strongest known zeitgeber could easily be used as therapeutic tool and could be optimized for photodynamic therapies in endodontics or light therapy for wound healing of periodontal tissues and oral mucosa. However, for this purpose the role of the circadian clock in the oral tissues needs to be understood. Besides new therapeutic approaches, assessment of patient chronotypes could improve treatment and diagnosis timings to save time, money and drug overload for the patient, altogether making medication more efficient. Recently the relation between a specific chronotype and bruxism was discussed, since bruxism can be assigned to different times of day. First results of clinical studies rather show a tendency to no correlation between chronotypes and bruxism.[86,87]

Circadian clocks are only one type of molecular clocks. There are also clock mechanisms for longer period intervals as for example circalunar clocks. These molecular clocks with longer time frames might be of interest for chronic diseases or diseases with a long time of development as cancer. These clocks are generally barely studied and completely unidentified in oral biology or dentistry. Further there are indications that molecular clocks play a role in aging[88] and forensics.[89,90] These specialties are not directly related with clinical dentistry, although could be interesting for the broad field of oral medicine.

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