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Table 1 Circadian clock findings in dentistry. Major findings in chronobiology connected to oral and maxillofacial surgery, restorative dentistry, endodontics, periodontics and orthodontics are listed here

From: Chronodentistry: the role & potential of molecular clocks in oral medicine

Field of dentistry

Molecule/Target

Major finding

Study model

Species

Reference

Oral & maxillofacial surgery

Clock, Bmal1, Tim, Cry1, Per1

oscillation in oral mucosa

in vitro/clinical

human

Bjarnason GA et al. (2001)

 

Bmal1, Cry1, Cry2, Per1, Per2, Per3, Ck1ε

dysregulation is associated with tumor development stage in head and neck squamous cell carcinoma

in vitro/in vivo

human/mouse

Matsumoto CS et al. (2016)

 

Per1, Per2, Dec1, Dec2, Cry1, Cry2, Npas2, Per3, Tim, Rorα, Rev-erbα

modulation is associated with cell proliferation, apoptosis and cell cycle progression in oral squamous cell carcinoma

in vitro

human

Wang Q et al. (2016), Zhao Q et al. (2016), Li H-X et al. (2016), Fu X-J et al. (2016)

 

Per, Tim

dysregulation is associated with tumor size, invasion and patient survival

in vitro

human

Hsu C-M et al. (2012)

 

Per1

association with tumor progression

in vitro

human

Chen R et al. (2012)

 

Per1

association with carcinogenesis

in vivo

hamster

Ye H et al. (2015)

 

Per1

association with later cancer stages and lymph node metastasis

in vitro/in vivo

human/mouse

Zhao N et al. (2013)

 

Per1

modulation by titanium in bone marrow stromal cells

in vitro

human/rat/ mouse

Hassan N et al. (2017)

 

Per1, Clock

recovery after surgery in head an neck squamous cell carcinoma patients with good prognosis

clinical

human

Hsu C-M et al. (2014)

 

Per2

potential tumor suppressor

in vivo

hamster

Tan X-M et al. (2015)

 

Per, Bmal1

association with tumor suppressor PTEN activity

in vitro/in vivo

human/mouse

Matsumoto CS et al. (2016)

 

Bmal1

dysfunction is associated with juvenile skeletal mandibular hypoplasia

in vitro/in vivo

human/mouse

Zhao J et al. (2018)

 

Tumor supressor genes Oncogenes

clock-controled genes in oral mucosa

in vitro

human

Zieker D et al. (2010)

Restorative dentistry

Clock, Bmal1, Per1, Per2

production in ameloblasts

in vitro/in vivo

rat/mouse

Zheng L et al. (2013)

 

Clock, Bmal1, Per1, Per2

varying production during tooth development

in vivo

mouse

Zheng L et al. (2011)

 

Per2

production in murine odontoblasts

in vivo

rat

Ohtsuka-Isoya M et al. (2001)

 

Bmal1

stimulation of Amelx and Klk4stimulation of Amelx and Klk4

in vitro

rat

Zheng L et al. (2013)

 

Bmal1

overexpression is associated with enamel morphology, thickness and hardness

in vitro

rat

Zheng L et al. (2013)

 

Amelx, Lamp1, Slc4a4, Car2

light period-dependent production

in vitro/in vivo

mouse/rat

Lacruz RS et al. (2012)

 

Ameloblast-specific genes Runx2

rhythmical production is associated with cell synchronization

in vitro

rat

Athanassiou-Papaefthymiou M et al. (2011)

 

Collagen

production follows a circadian rhythm and might contributes to the rhythmicity of incremental lines in dentin

in vivo

rat

Ohtsuka M et al. (1998)

 

Chronochemotherapy/ Chronoradiotherapy

reduction of adverse effects and stomatitis, improvement of treatment tolerance an survival time in oral squamous cell carcinoma and nasopharyngeal carcinoma

in vivo, clinical

mouse, human, mouse

Yang K et al. (2013), Zhang PX et al. (2018), Lin HX et al. (2013), Zhang Y et al. (2013)

 

cross-striations and incremental line

potential correlationswith circadian periodicity

in vivo, post mortem

mouse, human, monkey

Sehic A et al. (2013), Antoine D et al. (2009), Smith TM et al. (2006)

Endodontics

Clock, Bmal1, Per1, Per2

sporadical production in dental pulp cells

in vivo

mouse

Zheng L et al. (2011)

 

Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2

production by dental pulp-derived cells and modulation by hypoxic conditions

in vitro

human

Janjić K et al. (2018)

 

Bmal1, Per2, Rev-erbα Bmal1, Per2, Rev-erbα

mechanical stretching can synchronize clock components in dental pulp stem cells

in vitro

human

Rogers EH et al. (2017)

 

Per2, Per3

downregulation in dental pulps from carious teeth

in vitro

human

McLachlan JL et al. (2005)

 

pulp sensibility

might follow diurnal rhythms

clinical

human

Guo B et al. (2007)

 

pain sensation

possible correlation with circadian phases in oral region

clinical

human

Pöllmann L et al. (1987), Pöllmann L et al. (1978), Lemmer B et al. (1989), Lemmer B et al. (1991)

Periodontics

Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2

production in fibroblasts from gingiva and periodontal ligament and modulation by hypoxic conditions

in vitro

human

Janjić K et al. (2017)

 

Bmal1, Clock, Per1, Per2

produced in oral mucosa

in vitro/in vivo

human/mouse

Zheng L et al. (2012)

 

Clock:Bmal1 dimer

stimulation of SMAD3 promotor activity in gingival fibroblasts

in vitro/in vivo

human/mouse

Sato F et al. (2012)

 

Bmal1

increase of Agp5

in vitro/in vivo

human/mouse

Zheng L et al. (2012)

 

IL-1β

production in diurnal rhythms in crevicular fluid

clinical

human

Bergmann A et al. (2008)

 

periodontal indices

FMBS, FMPS, PSR and PRA show diurnal variations

clinical

human

Bertoldi C et al. (2017)

Orthodontics

Osteocalcin

promotor activity is regulated in an oscillatory manner in the maxillomandibular complex

in vivo

mouse

Gafni Y et al. (2009)