Implications of the circadian clock in implant dentistry.

Circadian rhythms are approximately 24-h cell-autonomous cycles driven by transcription and translation feedback loops of a set of core circadian clock genes, such as circadian locomoter output cycles kaput (Clock), brain and muscle arnt-like protein-1 (Bmal1), period (Per), and cryptochrome (Cry). The genetic clockwork of these genes produces circadian rhythms in cells throughout the body, including the craniofacial region. During development, dento-alveolar bone tissue formation could be regulated by site-specific circadian patterns. Studies using knockout mice and mesenchymal stem cells (MSCs) to evaluate clock genes revealed regulatory effects of clock function on bone remodeling, suggesting involvement of the circadian clockwork in osseointegration of titanium implants. Indeed, rough surface titanium modulates specific clock genes, Neuronal PAS domain protein-2 (Npas2) and Per, in MSCs to facilitate osseointegration. Further understanding of the bone clock machinery associated with biomaterial surface properties might improve preoperative diagnosis for dental implant treatments.